#BRAF Mutations Kit

[blackbiobiotech]

CMV Detection and BRAF Mutations: Advanced PCR Kits for Better Clinical Outcomes

In molecular diagnostics, accurate and efficient testing is paramount to understanding a variety of diseases, infections, and genetic conditions. Among the most important diagnostic tools are PCR kits, which are used to detect specific genetic material from pathogens or mutated genes. 3B BlackBio is a leader in providing advanced PCR-based diagnostic solutions with a wide range of products such as the CMV Detection Kit, Cytomegalovirus Detection PCR Kit, BRAF Mutations Kit, and BRAF PCR Kit. These kits have revolutionized the detection process and are essential in clinical diagnostics.

CMV Detection Kit: A Critical Tool for Early Diagnosis

Cytomegalovirus (CMV) is a virus that can affect individuals of all ages but poses a significant risk to immunocompromised individuals, such as those with HIV/AIDS or transplant patients. CMV can cause severe complications if not diagnosed early. The CMV Detection Kit by 3B BlackBio is designed to detect CMV infection at an early stage, allowing for timely treatment and management.

This PCR-based assay, which can be found at CMV Detection PCR Kit, utilizes quantitative techniques to assess viral load, enabling clinicians to monitor the progression of the infection. It offers high specificity and sensitivity, ensuring that even low levels of the virus are detected accurately. By providing reliable results, the CMV Detection Kit plays a pivotal role in improving patient outcomes and managing the virus effectively.

Cytomegalovirus Detection PCR Kit: The Science Behind Precision Diagnosis

The Cytomegalovirus Detection PCR Kit enhances the diagnostic process for CMV by allowing clinicians to detect the virus in a precise and efficient manner. This PCR kit is designed to identify the CMV genome in clinical samples, even when the viral load is low. This capability is particularly important in immunocompromised patients, where early detection is critical to preventing serious complications.

The PCR technique employed in this kit amplifies the CMV DNA, making it easier to detect and quantify. This high level of precision helps healthcare professionals not only diagnose the infection but also gauge the level of virus in the body. The real-time PCR system provides results quickly, facilitating faster decision-making in treatment plans. By using the Cytomegalovirus Detection PCR Kit, medical professionals can ensure that patients receive timely and appropriate care.

BRAF Mutations Kit: Understanding Genetic Mutations in Cancer

The BRAF Mutations Kit by 3B BlackBio is a critical diagnostic tool used in oncology for detecting BRAF mutations, which are commonly associated with various types of cancer, including melanoma, colon cancer, and thyroid cancer. BRAF mutations play a significant role in tumor development and progression, making the detection of these mutations vital for personalized cancer therapy.

The BRAF PCR Kit detects specific mutations in the BRAF gene, particularly the V600E mutation, which is frequently seen in cancers like melanoma. Identifying these mutations helps clinicians choose the most appropriate treatment options for patients, improving the chances of a successful outcome. This PCR-based test is highly sensitive, ensuring that even small amounts of mutated genetic material can be detected.

Through the BRAF Mutations Kit, 3B BlackBio provides a robust solution for oncologists to precisely monitor and treat patients with BRAF mutations. The early detection of these mutations enables more effective therapies, making this PCR kit a critical tool in personalized cancer treatment.

Why Choose 3B BlackBio’s PCR Kits?

3B BlackBio is a trusted name in the field of molecular diagnostics, offering innovative and reliable PCR kits that are essential for detecting viral infections and genetic mutations. Their products, such as the CMV Detection Kit, Cytomegalovirus Detection PCR Kit, BRAF Mutations Kit, and BRAF PCR Kit, provide high accuracy, sensitivity, and specificity. Whether for viral load detection or genetic mutation analysis, 3B BlackBio’s PCR kits are crucial in modern healthcare, helping clinicians make informed decisions to improve patient care.

[sandlerresearch]

Melanoma - Epidemiology Forecast to 2029 published on

https://www.sandlerresearch.org/melanoma-epidemiology-forecast-to-2029.html

Melanoma - Epidemiology Forecast to 2029

Melanoma – Epidemiology Forecast to 2029

Summary

Melanoma is a malignant neoplasm of melanocytes, the pigment cells in the skin located on the epidermis, the most superficial layer of the skin (World Health Organization, 2017). Melanocytes are embryological derivatives of neural crest tissue, and as such, any region of the body that is a derivative of the neural crest and contains melanocytes, namely areas of skin, meninges, mucous membranes, esophagus, and eyes, can develop melanoma (Komarnicky-Kocher and Alite, 2013). Accordingly, non-cutaneous melanomas typically occur in the eye and mucosa and account for only 4-5% of primary melanomas. This report focuses on melanoma of the skin (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] Code: C43) (Centers for Disease Control and Prevention, 2020; Mayo Clinic, 2020). Melanoma typically presents as a mole (nevus) on the skin, and is characterized by the growth’s asymmetry, irregular border, color variation, diameter greater than six millimeters, and evolution in appearance over a few weeks or months; these five diagnostic characteristics are known collectively by the acronym ABCDE (Gadeliya Goodson and Grossman, 2009; Goodman and Snyder, 2012).

In the 8MM, GlobalData epidemiologists forecast the diagnosed incident cases of melanoma to increase from 190,771 cases in 2019 to 222,458 cases in 2029, at an Annual Growth Rate (AGR) of 1.66%. The US will have the highest number of melanoma cases throughout the forecast period. The five-year diagnosed prevalent cases of melanoma in the 8MM are also expected to increase from 794,304 cases in 2019 to 947,373 cases in 2029 at an AGR of 1.93%.

Scope

– The Melanoma Epidemiology Report provides an overview of the risk factors and the global and historical trends for melanoma in the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Australia, and Canada). – The report includes a 10-year epidemiological forecast for the diagnosed incident cases of melanoma segmented by age (beginning at 18 years and ending at 85 years and older), sex, cancer stage at diagnosis (American Joint Commission on Cancer [AJCC] Stages I, II, III, and IV), and mutations (BRAF, BRAF V600E, BRAF V600K, BRAF Non-V600, NF1, BRAF/NF1, NRAS Q61, C-KIT, PD-L1 expression, tumor mutational burden [TMB], NTRK – mutations in tropomyocin receptor kinase [TRK]). – The melanoma epidemiology report is written and developed by Masters- and PhD-level epidemiologists. – The Epidemiology Report is in-depth, high quality, transparent and market-driven, providing expert analysis of disease trends in the 8MM.

Reasons to Buy

The Melanoma Epidemiology series will allow you to – – Develop business strategies by understanding the trends shaping and driving the global melanoma market. – Quantify patient populations in the global melanoma market to improve product design, pricing, and launch plans. – Organize sales and marketing efforts by identifying the age groups that present the best opportunities for melanoma therapeutics in each of the markets covered. – Understand magnitude of melanoma by stage at diagnosis and mutations.

[yourleonthomasme-blog]

Nublexa 40mg tablet - Apple pharmaceutical

Nublexa 40mg is an antineoplastic drug that prohibits Nublexa 40mg tablet price the growth and spread of cancer cells in the body.

Nublexa 40mg tab is needed to treat colorectal cancer and liver cancer. Nublexa 40 mg tablet  It is also needed to treat a rare type of tumor that can affect the esophagus, stomach, or intestines.

Nublexa 40mg tablet is commonly Nublexa 40 mg tablet given after other cancer regimens have been tried without success.

Nublexa 40mg is a prescription drug that is used under the supervision of medical practitioners.

INDICATION :

Nublexa 40mg tablet is indicated for the treatment of metastatic colorectal cancer (CRC) who have been Nublexa 40mg  previously treated with or are not considered candidates for, available therapies. These include fluoropyrimidine-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy (see section 5.1)

Nublexa 40mg tablet  tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib

Nublexa 40mg tablet price is indicated for the treatment of hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

DOSAGE: Colorectal cancer :

The  Nublexa 40mg usual dose is 160mg (four 40mg tablets) Po q Day for the first 21 days of each 28-day cycle.

Gastrointestinal stromal tumor :

The usual dose is 160mg Nublexa 40mg  (four 40mg tablets) Po q Day for the first 21 days of each 28-day cycle.

Hepatocellular carcinoma :

The usual dose is 160mg (four 40mg tablets) Nublexa 40mg Po q Day for the first 21 days of each 28-day cycle.

Follow the treatment of these conditions until disease progression or undesirable toxicity.Nublexa 40mg

MECHANISM :

Regorafenib belongs to oral Nublexa 40mg tumor deactivation agent which potently stops multiple protein kinases, contain kinases included in tumour angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis Nublexa 40mg  (KIT, RET, RAF-1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR) and tumour immunity (CSF1R). Regorafenib prohibits mutated KIT, a major oncogenic driver in gastrointestinal stromal tumors, and thereby stops tumor cell multiplication. In preclinical studies, regorafenib has described potent anticancer activity in a broad spectrum of tumor models containing colorectal, gastrointestinal stromal and hepatocellular tumor models which are likely mediated by its anti-angiogenic and anti-proliferative effects. In addition, regorafenib decreased the levels of tumor analog macrophages and has shown anti-metastatic effects in vivo. Major human metabolites (M-2 and M-5) displayed similar efficacies, compared to regorafenib in vitro and in vivo models.

DRUG INTERACTION

Nublexa 40mg concomitant use with strong CYP3A4 inducers will decrease Regorafenib plasma concentrations and increased plasma concentration of active metabolite M-2; M-5.

Nublexa 40mg interaction with strong CYP3A4 inhibitor will increase Regorafenib plasma concentration and reduced the plasma concentration of active metabolite M-2; M-5.

Nublexa 40mg interaction with BCRP substrate will increase the plasma concentration of the BCRP substrate.

MISSED DOSE

If a dose is missed, patients must consult with a medical practitioner and follow the instructions given by them. Thereby missed dose should be avoided and follow the regular dosing schedule

STORAGE

Store the Nublexa 40mg at 25℃ (77℃)

Keep the drug in its original container bottle

Keep the bottle tightly closed after one time used.

SIDE EFFECTS :

Common side effects occurring in greater than 30 %: Nublexa 40 mg tablet

Hand-foot syndrome , Diarrhea, Low platelets, Mouth sores/inflammation, Weight loss, Infection,  Nublexa 40 mg tablet Anemia, Increased liver enzymes (AST, ALT), Fatigue, High blood  Nublexa 40mg pressure, Voice disorder (Dysphonia), Protein in the urine, Low calcium, Nublexa 40 mg tablet  Low phosphorous, Low white blood cells, Decreased appetite, Increased lipase & amylase, High bilirubin in the blood, Low sodium, Nausea. Nublexa 40mg

Less common side effects occurring in about 10-29% of patients receiving  Nublexa 40mg :

Pain, Fever, Rash, Low potassium, Decreased blood clotting, Increased bleeding, Headache, Alopecia. Nublexa 40 mg tablet.

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Website: applepharmaceuticals

[cancersfakianakis1]

MEK inhibition may increase survival of NRAS-mutated melanoma patients treated with checkpoint blockade: Results of a retrospective multicentre analysis of 364 patients

Publication date: July 2018 Source:European Journal of Cancer, Volume 98 Author(s): Michael Constantin Kirchberger, Selma Ugurel, Johanna Mangana, Markus Valentin Heppt, Thomas Kurt Eigentler, Carola Berking, Dirk Schadendorf, Gerold Schuler, Reinhard Dummer, Lucie Heinzerling BackgroundMelanoma harbours genetic alterations in genes such as BRAF, NRAS and KIT. Activating NRAS mutations are present in about 20% of melanomas. Even though BRAF mutations can be effectively targeted with specific inhibitors, this approach has proven more challenging in cases of NRAS mutations. Previous reports suggested that immunotherapy might be more successful in NRAS-mutated compared to BRAF-mutated or BRAF/NRAS wildtype melanoma.Patients and methodsIn this study, overall survival and response to anti-PD-1 (nivolumab, pembrolizumab) and anti-CTLA-4 (ipilimumab) therapy of 364 patients with metastatic melanoma were assessed comparing 236 NRAS-mutated patients with 128 NRAS wildtype patients. Subtyping of NRAS mutation in 211 cases revealed 12 different genotypes of which Q61 mutations were predominant (95%).ResultsPatients with NRAS mutant melanoma showed similar response rates to checkpoint inhibitor therapy compared to NRAS wildtype patients with 15% versus 13% for ipilimumab (P = 0.731), 21% versus 13% for anti-PD-1 monotherapy (P = 0.210) and 40% versus 39% for ipilimumab and anti-PD-1 therapy in combination or sequence (P = 0.859). Nevertheless, median overall survival of patients with NRAS mutant melanoma was significantly lower with 21 months compared to 33 months in NRAS wildtype melanoma patients (P = 0.034). Therapy with oral MEK inhibitors before or after checkpoint inhibitor therapy showed a trend toward a survival benefit in patients with NRAS mutant melanoma.ConclusionsImmune checkpoint inhibition shows comparable response rates in NRAS-mutated and NRAS wildtype melanoma even though survival is less favourable in case of NRAS mutation. Additional MEK inhibition might improve clinical benefit. https://ift.tt/2xgbXvd

[chriscellman]

New Molecular Assay Kits are Designed for Detection of BRAF Mutations

Switch-Blocker technology provides the ability to block normal DNA and analyze target area of interest Offer sensitivity compared to NGS-based biomarker analysis for detection of key actionable oncogene mutations from blood sample Detect key oncogene mutations through analysis of Formalin-Fixed Paraffin-Embedded (FFPE) tissue gained from surgical biopsies and circulating tumor DNA (ctDNA) gained from blood-based liquid biopsies This story is related to the following: Test & Measuring Instruments Search for suppliers of: Diagnostic Test Kits from HVAC /fullstory/new-molecular-assay-kits-are-designed-for-detection-of-braf-mutations-40036004 via http://www.rssmix.com/

[juniperpublishers-endocrinology]

Diagnostic Value of High Resolution Neckultrasongraghy, Fine Needle Aspiration Cytology and BRAFV600E Mutation in Diagnosis of Malignant Thyroid Nodules- Juniper Publishers

Abstract

Background: Thyroid malignancy is rapidly raising, nearly 9-15% of the thyroid nodules are malignant nodules. Finding an optimal mean to diagnose malignant thyroid nodule preoperative is a challenge. Combination of molecular analysis, imaging and cytopathology may be helpful. This study aimed to evaluate the value of adding BRAFV600E analysis to nodules with suspicious ultra-sonographic criteria.

Patients and methodology: 50 patients from Kasr alainy endocrine outpatient clinic with solitary or multiple thyroid nodules are included, All patients subjected to full history and examination, thyroid profile, high resolution neck High resolution neck ultrasound (U/S), Fine needle Aspiration Cytology (FNAC), U/S guided FNAC and BRAFV600E analysis on FNAC using DNA sequencing then high resolution melt curve analysis (HRMA) for confirmation.

Results: The incidence of BRAFV600E mutation among papillary thyroid cancer (PTC) patients was 55.6%. it’s sensitivity 42.9%, specificity was 100% in diagnosing PTC. Sensitivity of high resolution neck ultrasonograghy in detecting malignancy was 88.2%, specificity 72.7%. Addition of ultrasonography to BRAFV600E analysis increased ultrasound sensitivity in detecting PTC preoperative to 92%. There was a positive correlation between most suspicious ultrasonography findings and presence of BRAFV600E mutation (increased AP/T diameter, Increase intra-nodular blood flow, cervical lymphadenopathy, absent or incomplete halo (all p value<0.001), irregular border p value 0.004, micro calcifications p value 0.007.

Conclusion: Adding BRAF-V600E analysis to work up of suspicious thyroid nodule would increase the sensitivity of preoperative diagnosis of PTC especially in cases of indefinite pathological findings. HRMA is simple, low cost tool for BRAF-V600E analysis in comparison to DNA sequencing method.

Keywords:Thyroid nodule; Thyroid cancer; High resolution neck ultrasound (U/S); Fine needle aspiration cytology (FNAC); BRAFV600E mutation

Abbreviation:(U/S): High Resolution Neck Ultrasound; FNAC: Fine Needle Aspiration Cytology, PTC: Papillary Thyroid Cancer; HRMA: High Resolution Melt Curve Analysis

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Introduction

Thyroid nodules are a common problem their prevalence reaching 35% by ultrasound examination in some studies [1] and 8-65% in autopsy data [2] There is an increasing rate ofthyroid cancer incidence worldwide, There is an increasing rate of thyroid cancer incidence worldwide. 9~15 % of all thyroid nodules are malignant [3,4]. Accordingly the initial evaluation of thyroid nodule should focus on exclusion of malignancy [3].

High resolution U/S is the most sensitive diagnostic imagingtechnique for the detection of the thyroid nodules [4], it cancharacterize suspicious nodules by some sonographic [5], but itdepends on the skills and accuracy of the operator [6].

FNAC is the most important step in the work up of thethyroid nodule; Diagnostic accuracy has improved using USneedle localization due to a decreased number of inadequatespecimens and false negative results [7]. The pathology reportfrom FNAB according to Bethesda may be read as non-diagnostic,benign, indeterminate lesion (atypia or follicular lesion ofundetermined significance), Follicular neoplasm or suspiciousfor follicular neoplasm, Suspicious for malignancy and malignant[8,9]. Benign lesions on FNAB have an approximate 3% risk ofmalignancy (vary with patient population), and may be followedclinically with ultrasound or with a repeat FNAB [9], which, ifalso benign, decreases the risk of a false negative to 1.3% [10],the only malignant pathology reliably diagnosed through FNABis papillary thyroid carcinoma, as features such as ‘OrphanAnnie’ nuclei, nuclear grooves, intra-nuclear inclusions, andpsammoma bodies can be sufficient for a diagnosis [11]. Benignand malignant follicular neoplasms and oncocytic (Hurthle cell)adenomas and carcinomas cannot be distinguished on the basisof cytology alone, as tissue architecture is required to make thediagnosis of malignancy through observation of capsular orangio-lymphatic invasion [12].

Indeterminate cytology findings vary from 15% to 25%[13]. Indeterminate FNAC results and cyto-diagnostic errors areunavoidable due to overlapping cytological features particularlyamong hyperplastic adenomatous nodules, follicular neoplasmsand follicular variants of papillary carcinoma [14]. Thecorrelation of U/S features with FNAB results helps to overcomethe limitations of FNAB alone [15] even when cytological resultswere the same, the malignancy rate was higher when noduleshad suspicious U/S findings [16], So, U/S features and FNABresults are complementary to each other [17].

From that comes the importance of a new diagnostic toolto solve the problem, to overcome the limitations of FNA and toavoid unnecessary surgery. Several molecular factors have beenadded to improve the diagnostic accuracy of U/S-guided FNAB[2,18] one of the promising genetic factors is the analysis of theV600E mutation [19,20].

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Aim Of The Work

To detect an accurate and useful tool for early preoperativedetermination of thyroid malignancy in the patients with thyroidnodule and assess its value in addition to the previous modalities(ultrasonography, and FNAC) that may increase the diagnosticaccuracy and prevent unnecessary surgery

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Patients And Methods

This single group comparative descriptive study included50 patients from Kasr Alainy endocrine outpatient clinic, CairoUniversity.The thyroid examined contained either solitaryor multiple nodules. Four patients with four nodules werehypothyroid (8%), and two nodules were in hyperthyroidpatients (4%), and the remaining part 44 nodules were ineuthyroid patients (88%).18 examined nodules were solitarynodule and 32 were a nodule in MNG. Nodules’ size ranges from0.6-28mm3, Mean 6.6mm3±5.8mm3 SD, Median 6.0mm3. Patients’ages ranged from 22-65 years old median 43.0±9.6 SD, Median43.5. five males (10%) and 45 females (90%). Demographic dataare included in Table 1.

All patients were subjected to

Full clinical history including age, sex, past historyof head and neck irradiation and positive family history ofthyroid cancer.

Thyroid examination.

Thyroid profile (FT3, FT4, and TSH).

High resolution neck ultrasound.

U/S guided FNAC.

BRAFV600E analysis.

Ethical considerations

All patients were informed about these types of investigationsand for confidentiality their names were omitted and replacedby numerical codes.

Sonographic criteria for thyroid nodules include

Echogenicity, Presence or absence of calcification and itstypes, A-P to Transverse diameter ratio, Blood flow in the noduleand its patterns whether central or peripheral or both, Solitaryor dominant nodules, Presence or absence of halo, Solid, cystic orpartially solid and partially cystic, Sharpness of border.

Signs of increase risk of malignancy in U/S include

Hypo-echogenicity. Micro- or interrupted rimcalcifications, Irregular Margins.

Absence of Halo or incomplete halo.

Increased Intra-nodular flow.

Increase antro- posterior to transverse diameter(AP/T) diameter.

Significant increase in size over time.

Invasion of anterior strap muscles

Presence of abnormal cervical lymphadenopathy.

All cytology specimens were obtained under ultrasoundguidance using a 21-gauge needle attached to a plastic syringe,part of the smear obtained were wet fixed in 95% ethyl alcoholand stained with hematoxylin and eosin stain for routinecytological evaluation, and the other part put in test tube withsaline for genetic examination.

Molecular genetic testing

Specimen collection: Samples were collected from eachsubject in sterile containers for the genotyping technique.Samples were either processed fresh or were stored at 2-8 °C.

DNA extraction: This was performed using ThermoScientific Gene JET Whole Blood Genomic DNA Purification MiniKit supplied by Thermo Scientific Fermentas. The extractedDNA then subjected to the algorithm for molecular detectionof BRAFV600E mutation. The aim of the current study is thedetection of the most common mutation in the BRAF gene.V600E in DNA samples collected from thyroid nodules.

We used DNA sequencing method for BRAF V600E mutationdetection, unfortunately all samples were BRAF V600E mutationnegative, so we tried more accurate method (HRMA), then DNAsequencing for validation of the mutant BRAF results had done.

The extracted DNA were conducted to the work asfollows

Extracted DNA DNA sequencing of exon 15 HRMA DNAsequencing for validation of the mutant BRAF results

DNA amplification using the polymerase chainreaction

DNA amplification using the PCR: Enzymatic amplificationwas performed by PCR using HotStarTaq® Master Mix Kit (250units) supplied by QIAGEN® and BIO RAD T100TM ThermalCycler*.

Detection of PCR amplification products: Fluorescentstained DNA was detected by using Agarose Gel Electrophoresisand Ultra-Violet Light Trans-illumination.

Purification of PCR product: This was performed usingQIAquick® PCR Purification Kit supplied by QIAGEN® (Table 2).

Sequencing coding sequence and intronic boundaries ofExon 2 and Exon 3 in INS gene Cycle Sequencing: Using theApplied Biosystems* (ABI) PRISM® BigDye® Cycle SequencingReady Reaction Kit.

Second purification: Removal of excess Dye DeoxyTMterminators from sequencing reactions by using Centri-Sepcolumns (Princeton separations) Terminator v3.1 CompletedDNA long Read capillary electrophoresis on the ABI 3500.

Analysis of data

Sequences were compared to the published Referencesequence of Homo sapiens (BRAF), NCBI (National Centre ofBiotechnology Information): (NG_007873.3, NM_004333.4,and NP_004324.2) Analysis was done by BLAST (Basic LocalAlignment Search Tool) (www.ncbi.nlm.nih.gov) and the CLCBIOsequence viewer 6 program (www.clcbio.com ).

High resolution melt curve analysis: The HRMA reactionwas done according to the protocol of the kit MeltDoctor TMHRM Master Mix Applied Biosystems, USA.

DNA sequencing for validation of the BRAF mutantresults: The samples with mutant results were processed afterHRM analysis by pipetting the reaction from the reaction tubesfollowed by purification of the products.

Statistical analysis: Pre-coded data was entered on thecomputer using “Microsoft Office Excel Software” program(2010) for windows. Data was then transferred to the StatisticalPackage of Social Science Software program, version 21 (SPSS) tobe statistically analyzed.

Data was summarized using range, mean, standard deviationand median for quantitative variables and frequency andpercentage for qualitative ones. Comparison between groups wasperformed using independent sample t-test or Mann Whitneytest for quantitative variables and Chi square or Fisher’s exacttest for qualitative ones. P values less than 0.05 were consideredstatistically significant, and less than 0.01 were consideredhighly significant.

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Results

There is no statistically significant association betweendifferent sex, nodular site, count and thyroid functions withmalignancy or BRAFv600E gene mutation (Table 3). Pathologyresults showed 28 benign nodules, 17 malignant nodule (12papillary -5 follicular neoplasm) and 5 cases with indefinitenodules. The incidence of BRAF V600E gene mutation in ourpatients with PTC was 55.6%

50 nodules were included but unfortunately because ofrepetition of genetic analysis for BRAF V600E gene mutations byDNA sequencing then again by HRMA methods that leads to that3 samples were not enough to complete genetic analysis so BRAFV600E analysis completed only in 47 samples.

We found a positive correlation with significant p valuebetween some suspicious sonographic criteria and malignancyand some suspicious sonographic criteria and BRAF V600Emutation as increased (AP/T) diameter, absent or interruptedhalo, micro-calcifications, increase intra-nodular blood flow,presence of suspicious LNs and irregular border with increasedboth sensitivity and specificity (Table 4 & 5).

Six malignant nodules were found to harbor BRAF V600Egene mutation, five of them were papillary thyroid carcinomaand one was follicular neoplasm by FNAC with P value 0.001 andnothing was found in benign nodules so there was significantcorrelation between BRAF V600E gene mutation and papillarythyroid cancer. Overall, sensitivity of ultrasound in detectingmalignancy was found to be 88.2%, specificity 72.7%, Sensitivityof US and BRAF V600E mutation combined was 92% (Table 6).

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Discussion

It is noticed that thyroid nodules more common finding infemales more than males, Framingham survey for thyroid nodulesshows that prevalence in females 6.4% and 1.5% in males, andthe Whickham study displays (6.6:1 ratio females /males)[21], This might explain why most of the patients in our studywere females representing 90%. The incidence of malignancyin our study was 34% this result is biased because 12 nodulesdiagnosed as PTC are chosen retrograde after diagnosis of PTCto assess BRAF v600E mutation status.

The incidence of BRAF-V600E gene mutation in our patientswith PTC was 55.6%; previous meta-analyses have publishedvalues for the overall prevalence of the BRAF-V600E mutationin PTC ranging from 29 to 83%. [10,22,23], this wide rangemay be due to variations in PTC subtype, subjects’ geographicalbackgrounds, and research methodology.

No difference in BRAFV600E gene mutation incidencebetween different age groups and this shows agreement withAh Young Park et al. [24], but regarding our result of absenceof significant association of BRAFV600E gene mutation withspecial sex that shows disagreement with Ah Young Park et al.study that shows increase mutation in male sex, this may be dueto the small number of cases involved in our study, also 90% ofour cases are females that cannot reflect the actual prevalence[24].

Our study contained five nodules (10%) with undeterminedcytology, four of them have suspicious US features and all werenegative regarding BRAF-V600E gene mutation, we can’t excludemalignancy in these cases by absence of BRAF-V600E genemutation alone as BRAF-V600E mutation is found only in nearly40% of PTC cases [25].

The presence of BRAF-V600E mutation in one case offollicular neoplasm out of five cases shows agreement with onlyone case report Pennelli et al. [26], this conflicting result maybe due to inadequate cytological diagnosis and interpretationas follicular variant of papillary cancer may be interpreted as amicro follicular lesion in FNA [27], so this case need follow upand pathological confirmation post thyroidectomy to make sureof this result.

In this present study BRAF-V600E mutation was negativein benign cases, this result shows agreement with other studies[10,11] and BRAF-V600E mutation is believed to be specific forPTC because no report has been issued of this mutation in benignnodules [28].

The sensitivity of BRAF-V600E gene mutation in detectingPTC was 42.9%, specificity was 100%, positive predictive value100%, and accuracy 83%, this result shows agreement with Kimet al that shows BRAF-V600E mutation alone has a specificityof 100% and a positive predictive value of 100% for diagnosingmalignancy in PTC [9,29].

Nam et al. [30] reported significant improvements in thesensitivity, negative predictive value, and diagnostic accuracy ofFNA cytology for diagnosing malignancy by adding BRAF-V600Eanalysis to both US and FNAC [30].

Several studies have found a positive correlation betweenthe BRAF-V600E mutation and suspicious sonographic featuresof thyroid nodules [7], other studies show inconsistent results;Kwak, et al. found that only marked hypo echogenicity wasassociated with BRAF-V600E positivity, Hwang et al. found thatonly calcification was associated with BRAF-V600E positivity[29,31] both these studies predominantly evaluated smallpapillary thyroid micro carcinomas, with mean tumor sizesof 6-9mm3, the small size was likely a significant confoundingfactor in characterizing these lesions by preoperative US.

Our study shows positive correlation between mostsuspicious US findings and BRAF-V600E gene mutation andshows that AP/T≥1, absent or incomplete halo, irregular border,micro-calcifications and Increase intra-nodular blood flow havepositive correlation with positivity of BRAF-V600E mutationthese results show agreement with Kabaker et al. [32] thatshowed association of BRAF-V600E positivity with most knownsuspicious U/S finding including taller than wide shape, illdefinedmargin, hypo-echogenicity, micro-calcifications andabsent halo (p value<0.001) [32].

This study also showed that BRAF-V600E gene mutation issignificantly present in cases with cervical lymphadenopathythis result shows agreement with many studies that correlateBRAFV600E gene mutation with the frequency of lymph nodemetastases [10,22] Park et al. [24] study concluded that theBRAF-V600E mutation was associated extra-thyroidal extension,central and lateral lymph node metastasis, and advanced tumorstage (P<0.0001, so BRAFV600E analysis preoperative may be ofvalue as prognostic marker and affect surgical decision regardingtype of surgery.

DNA sequencing method shows high cost, time consumingand low sensitivity for the clinical screening of BRAF V600Emutation and this shows agreement with other study [33] thatshows accuracy of DNA sequencing is low when dealing withcytological specimens where the cells in question may be aminor population among the vast majority of background nonneoplasticcells, Furthermore, this method needs expensiveequipment which may not be economical for all the patients[34], In contrast HRMA has been proved to be applicable, costefficientand very sensitive scanning method that allows rapiddetection of DNA sequence variations without cumbersomepost–polymerase chain reaction (PCR) methods, which is notachievable by direct sequencing [35]. Because targeted therapyfor thyroid cancers with multikinase inhibitors is under activedevelopment [36,37], the detection of mutations in the FNACmaterial may be helpful in the future to guide mutation-specifictargeted therapies that can be initiated preoperatively or inthose patients who are not surgical candidates. This study hassome limitations as small number of patients included, somegenetic mutations should be included as RAS and RET and RET/PTC rearrangement.

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Conclusion

BRAFV600E positivity was associated with most knownsuspicious U/S finding, BRAFV600E gene mutation analysisis a new hopeful diagnostic and prognostic tool that helps toovercome limitations of high resolution neck ultrasonographyand fine needle aspiration biopsy, Adding BRAF-V600E analysisto U/S and FNA would increase the sensitivity of preoperativediagnosis of PTC especially in cases of indefinite nodules. HRMAis an excellent, simple, low cost tool for BRAF-V600E analysis incomparison to DNA sequencing method.

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For more articles in Journal of Thyroid Research please click on: https://juniperpublishers.com/jetr/index.php

[pharmamktnet]

GENECAST Launches BRAF Mutation Test Kits with the Highest Detection Sensitivity 0.0001%

GENECAST Launches BRAF Mutation Test Kits with the Highest Detection Sensitivity 0.0001%

SEOUL, South Korea–(BUSINESS WIRE)–<a href="https://twitter.com/hashtag/ADPS?src=hash&quot; target="_blank">#ADPS</a>–GENECAST, cancer diagnostics company through liquid biopsy, launched BRAF mutation test kits with the highest detection sensitivity 0.0001%. http://www.businesswire.com/news/home/20190617005007/en/GENECAST-Launches-BRAF-Mutation-Test-Kits-Highest/?feedref=JjAwJuNHiystnCoBq_hl-WBlL…

[azveille]

Mélanome : intérêt médico-économique d'un test génétique non invasif des lésions suspectes

Un kit de biopsie cutanée sous la forme d'un patch adhésif permet l'analyse génétique de lésions pigmentées suspectes pour identifier le risque de mélanome, avec un coût réduit par rapport à l'évaluation visuelle suivie d'une analyse histopathologique, suggèrent des études présentées au congrès de l'American Academy of Dermatology (AAD), qui s'achève mardi à San Diego.

Dans un communiqué dimanche, DermTech a annoncé le lancement de Nevome*, son dispositif de biopsie cutanée par patch adhésif dans l'aide au diagnostic des mélanomes, sur la base de l'étude de validation présentée en session late-breaking, samedi.

La société américaine développe à la fois un kit de biopsie cutanée sous la forme d'un patch adhésif, qui permet de collecter des échantillons de couche cornée. Ceux-ci peuvent ensuite être envoyés à DermTech pour analyse des ARN notamment.

Dans l'étude présentée samedi, DermTech rappelle que le test qui analyse l'expression des gènes LINC et PRAME dans des lésions pigmentées présente un taux de sensibilité de 91% et de spécificité de 69% et a démontré sa validité par rapport à l'analyse histopathologique.

Cette fois, il s'agissait d'évaluer la validité du test par rapport à l'analyse des "point chauds" mutationnels dans les gènes BRAF, NRAS et TERT, qui ont été associés à des critères histopathologiques de progression du mélanome.Une analyse rétrospective a été réalisée pour rechercher les mutations BRAF, NRAS et TERT dans 103 mélanomes diagnostiqués par consensus d'experts sur données histopathologiques à partir d'échantillons recueillis prospectivement avec le patch adhésif.

Des résultats positifs ou négatifs pour les mutations recherchées ont été obtenus pour 97% des échantillons. La fréquence des mutations était de 75% pour les échantillons positifs pour les points chauds mutationnels, contre 15% pour les échantillons négatifs, soit une différence statistiquement significative.

Les mutations identifiées dans les échantillons prélevés à l'aide du patch adhésif étaient concordantes avec celles présentes dans les préparations de tissus pour l'analyse histopathologique. Les mutations du gène TERT étaient les plus fréquentes (79%).

Une analyse prospective a ensuite été réalisée sur 523 échantillons prélevés avec le patch adhésif en pratique clinique: parmi ceux avec des résultats négatifs, 89% n'avaient pas les points chauds mutationnels et parmi les résultats positifs, 60% avaient bien les points chauds mutationnels.Les résultats étaient concordants entre les échantillons de validation et ceux issus de la vraie vie et confirment "la performance élevée" du test génétique, conclut DermTech.

Dans une autre étude présentée au congrès, la société américaine a voulu estimer les économies potentielles générées par l'usage de son test par rapport à l'approche recommandée actuellement, associant évaluation visuelle de la lésion et analyse histopathologique.

Pour cela, ils ont estimé que du point de vue du payeur aux Etats-Unis, à partir des tarifs des centres Medicare et Medicaid, le recours au kit de biopsie par patch adhésif permet une réduction du coût de 395 $ pour un patient par rapport à une procédure nécessitant une biopsie classique suivie d'une excision de la lésion.

En évitant les délais de prise en charge liés à des faux négatifs, les coûts de traitement peuvent être diminués de 433 $ en utilisant le patch adhésif, par rapport à la procédure classique.

Globalement, ces résultats suggèrent que le test génétique d'un échantillon prélevé par patch adhésif permet d'éviter des actes et des consultations, sans retarder la détection du mélanome, et potentiellement de réduire les coûts directs de prise en charge, conclut la société.

Une troisième étude était présentée, sur l'intérêt de l'analyse génétique pour l'identification des cancers cutanés non mélanomes, des carcinomes épidermoïdes et des carcinomes baso-cellulaires. A partir de 160 échantillons, le modèle développé a permis de différencier ces deux types de carcinome des kératoses actiniques et des autres lésions cutanées non cancéreuses avec une sensibilité de 91% et une spécificité de 87%.

Ce test est à présent en cours de validation dans une large étude prospective.

[jeramyalba52580-blog]

Scientific Tests For Three-way

The work important misuse prevention coalitions is closely connected to hygienics. GSS builds durable, certified, actionable specimen pipelines for research study today and in the future. Laboratories set up a limit pertaining to the portion of tissues which stain along with the antitoxin. Sibling modification to youth cancer joint research: health and wellness end results from siblings of kids with cancer cells. Boob as well as cervical cancer assessment inquiries belonged to the core questions carried out in all conditions.

Mei JV, Alexander R, Adam BW, et cetera. Use of filter paper for the assortment and evaluation from individual whole blood samplings. Outcomes: A bulk of markers were actually observable in over 25% from people on all sampling types/kits. Cancers of the bowel, like those of the bust as well as uterine cervix, are good intendeds for early medical diagnosis due to the fact that they are frequently preceded by preneoplastic lesions that generally have a lengthy natural history. Kaposi WGA DNA compilation: The ACSR built a KS tissue microarray and sections apiece from those diagnostic biopsies (119 instances) were made use of for WGA production. The compilation carries 168 fish specimens comprising primarily of dried skins coming from one side combining one-half from the skeleton. It was accordinged to the principle of boob tissue getting older as the origin from breast cancer. Various other sociodemographic aspects including brother or sister grow older, informative achievement, as well as health plan status were related to skin cancer cells prevention practices. Building specimen allowance plans to decrease the influence of this particular sort of variability is crucial for obtaining valid and dependable lead to longitudinal studies (2 -4, 6 ). Impact: The presence of a BRAF c. 1799T > A (p.V600E) mutation is actually linked with significantly poorer diagnosis after CRC diagnosis one of subgroups of individuals. Lead the Job's public relations efforts and preserve connections across the international press, news, as well as associated media channels for the Venture. Just 14 per-cent of those discharged off an overall medical facility who later died by self-destruction had gotten a psychological prognosis in the course of their last visit. Patients who possessed an interval intestines cancer cells showed no evidence of even worse quality of life, clinical depression, or even perceived problem in possessing their cancer diagnosed, than patients that had certainly not been invited for testing, however they performed have worse quality of life and also greater viewed problem, compared to clients who acquired a screen-detected prognosis. Our company used Cox regression to analyze the affiliation between BRAF c. 1799T > A (p.V600E) anomaly condition and also survival after CRC diagnosis, where the moment axis was defined as times given that medical diagnosis. Gebbia assisted introduce the Away from the Night Walks to rear understanding and also funds for self-destruction avoidance. At my job diabetes mellitus is a huge trouble and our experts desire to start taking measures to decrease this as well as help improve employee's health. Furthermore, The Skin layer Cancer Base thinks about tanning to become old-fashioned and also obsolete as a way of living. The Governor's Protection Collaboration greatly values Comcast's on-going help as well as devotion to the essential youth deterrence problems impacting Connecticut's young people. Safeguard, trusted, real-time digital specimen tracking ensures the amount of time as well as information spent gathering actionable data is actually not dropped. Longnecker M. P. Alcohol consumption in relation to jeopardize of bust cancer cells: meta-analysis and also assessment. McCarthy EP, Burns RB, Coughlin SS, et cetera. Mammography use assists to reveal differences in bosom cancer cells stage at diagnosis in between much older white and black girls. Omitting one person who Scope sampling evaluated unfavorable whatsoever 3 time factors and also the PreservCyt sampling tested positive in all three time aspects (Fig. Occurrence of sports and recreation related traumas resulting in a hospital stay in Wisconsin in 2000. Anti-estrogen therapy starting in the year after diagnosis (yes or no; Supplementary Table S1) was recognized using PCRS prescribed records. The market value from modern mammography testing in the command of breast cancer cells: knowing the supports from the current debates. Principle: The source presents 12 attribute from personal injury rows and 36 physical body location rows placing each ICD-9-CM code in the variety from 800 to 995 in an one-of-a-kind tissue location in the source. If you cherished this article so you would like to get more info with regards to http://psychoapphealth.info/ nicely visit our own web page. While more analysis on several of the more recent methods remains to become done, each one of these approaches must be looked at when you are actually checking out methods to stop skin cancer.

[gobidbargir]

پاسخ داده شده: آدرس و تلفن بهترین آزمایشگاه مجهز در شهر شیراز کجاست؟

https://ift.tt/2sw85VH,

سلام

تو شیراز آزمایشگاه های زیادی هست، ولی یه آزمایشگاه خوب نزدیک بیمارستان سعدی هست که کلیه خدمات آزمایشگاه (هماتولوژی، پاتولوژی، تست بارداری، آزمایش خون، آزمایش ادرار و...) رو به صورت مجهز با قیمت مناسب انجام میده. مشخصاتش رو اینجا می فرستم:

آدرس: شیراز، بلوار زند، ابتدای 20 متری سینما سعدی (خیابان هفت تیر)، ساختمان شیراز نقش، طبقه اول

تلفن: 07132337063 - 07132304834

موبایل: 09023853737 - 09023854747

  لیست آزمایش هایی که انجام میدن رو هم اینجا می فرستم:

Hematology

Clinical Biochemistry

Urine analysis & Microbilogy

Hormonology(endocrinology)

Performed by Electro-Chemi Luminescence (ECL) method

Pregnancy Screening Test

Double Marker, Quad Markers, AFP, Non-Invasive prenatal testing (NIPT)

Coagulation

Factor V, Protein C, Protein S, D-Dimer, Anti-thromin III, Fibrinogen

Tumor Marker Detection

βHCG , CA 125, PSA , Free PSA, CEA, CA 19-9, CA 15-3, CA 242, CA 7-24, ……

Auto Immune disease detection

Immunoassay test performed to detect Auto AB against Several Ag such as ANA, ds-DNA, CCP, ANCA (C & P), B2 glycoprotein, ASMA, Anti-SLA, Anti-GAD Ab, …….

Infectious  Disease Detection

HPV genotyping (37 genotype), Immunoassay for detection microbial Ag/Ab, PCR detection for HBV, HCV, CMV, EBV,VZV, Rubella,  BK & JC viruses, Brucella, Aspergillus

Flow cytometry

Detection all CD marker for Determination all Lymphocyte Subsets

TDM & Drug monitoring

Detection more than 5o drug in urine of patients

Transplantation Immunology

High-Resouloution HLA Typing, HLA Class I & II detection, Disease related HLA detection (PCR based Method)

Cancer Pharmacogenomics Tests

BCR-ABL translucation, Her2/neu amplification (FISH), EGFR mutation, ALK mutation, BRAF mutation, K-ras mutation, N-ras mutation, c-KIT mutation, MLH1 Mutation, p53 mutation, BRCA1, BRCA2

Pathology & Cytology

Pathology, Cytology, Pap-smear, Immunohistochemical studies (IHC)

[yourleonthomasme-blog]

Stivarga 40mg -Regorafenib

Stivarga 40mg

Stivarga 40mg is an antineoplastic drug which prohibit with the growth and spread of cancer cells in the body.

Stivarga 40mg is needed to treat colorectal cancer and liver cancer. It is also needed to treat a rare type of tumor which can affect the oesophagus, stomach, or intestines.

Stivarga 40mg is commonly given after other cancer regimens have been tried without success.

Stivarga 40mg is a prescription drugs which is used under the supervision of medical practioners.

INDICATION :

Stivarga 40mg is indicated for the treatment of metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies. These contains fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy (see section 5.1)

Stivarga 40mg tablet  is indicated for the treatment of unresectable or metastatic gastrointestinal stromal tumours (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib

Stivarga 40mg tablet is indicated for the treatment of hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

DOSAGE :

Colorectal cancer :

Stivarga 40mg tablet  The usual dose is 160mg (four 40mg tablets) Po q Day for the first 21 days of each 28-day cycle.

Gastrointestinal stromal tumor :

The usual dose is 160mg (four 40mg tablets) Po q Day for the first 21 days of each 28-day cycle.

Hepatocellular carcinoma :

The usual dose is 160mg (four 40mg tablets) Po q Day for the first 21 days of each 28-day cycle. Stivarga 40mg tablet

Follow the treatment of this conditions until disease progression or undesirable toxicity. Stivarga 40mg tablet

stivarga 40mg

MECHANISM :

Stivarga 40mg Regorafenib belongs to oral tumour deactivation agent which potently stops multiple protein kinases, contain kinases included in tumour angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR) and tumour immunity (CSF1R). Regorafenib prohibits mutated KIT, a major oncogenic driver in Stivarga 40mg gastrointestinal stromal tumours, and thereby stops tumour cell multiplication. In preclinical studies regorafenib has described potent anticancer activity in a broad spectrum of tumour models containing colorectal, gastrointestinal stromal and hepatocellular tumour models which is likely mediated by its anti-angiogenic and anti-proliferative effects. In addition, regorafenib decreased the levels of tumour analogue macrophages and has shown anti-metastatic effects in vivo. Major human metabolites (M-2 and M-5) displayed similar efficacies, compared to 

for more infowmation :  Stivarga 40mg, Stivarga 40mg tablet,  Stivarga 40mg tablet,

[cancersfakianakis1]

Analysis of mucosal melanoma whole-genome landscapes reveals clinically relevant genomic aberrations

Purpose: Unlike advances in the genomics-driven precision treatment of cutaneous melanomas, the poor current understanding of the molecular basis of mucosal melanomas (MMs) has hindered such progress for MM patients. Thus, we sought to characterize the genomic landscape of MM to identify genomic alterations with prognostic and/or therapeutic implications. Experimental Design: Whole-genome sequencing (WGS) was performed on 65 MM samples, including 63 paired tumor blood samples and 2 matched lymph node metastases, with a further ddPCR-based validation study of an independent MM cohort (n = 80). Guided by these molecular insights, the FDA-approved CDK4/6 inhibitor palbociclib was tested in a MM patient-derived xenograft (PDX) trial. Results: Besides the identification of well-recognized driver mutations of BRAF (3.1%), RAS family (6.2%), NF1 (7.8%) and KIT (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene POM121 (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations (SVs) between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (CDK4, MDM2 and AGAP2) at 12q13-15, and this co-occurred significantly with amplification of TERT at 5p15,-which-was-verified-in-the validation cohort; (iv) the PDX trial demonstrated robust anti-tumor effects of palbociclib in MMs harboring CDK4 amplification. Conclusions: Our largest-to-date cohort WGS analysis of MMs defines the genomic landscape of this deadly cancer at unprecedented resolution, and identifies genomic aberrations that could facilitate the delivery of precision cancer treatments.

http://bit.ly/2Ei1aSJ

[cancersfakianakis1]

Targeted Therapy and Immunotherapy for Melanoma in Japan

Opinion statement

Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10–15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.

http://bit.ly/2FJUC1t

[cancersfakianakis1]

The identification of patient‐specific mutations reveals dual pathway activation in most patients with melanoma and activated receptor tyrosine kinases in BRAF/NRAS wild‐type melanomas

Background

Increasing knowledge of cancer genomes has triggered the development of specific targeted inhibitors, thus providing a valuable therapeutic pool.

Methods

In this report, the authors analyze the presence of targetable alterations in 136 tumor samples from 92 patients with melanoma using a comprehensive approach based on targeted DNA sequencing and supported by RNA and protein analysis. Three topics of high clinical relevance are addressed: the identification of rare, activating alterations; the detection of patient‐specific, co‐occurring single nucleotide variants (SNVs) and copy number variations (CNVs) in parallel pathways; and the presence of cancer‐relevant germline mutations.

Results

The analysis of patient‐matched blood and tumor samples was done with a custom‐designed gene panel that was enriched for genes from clinically targetable pathways. To detect alterations with high therapeutic relevance for patients with unknown driver mutations, genes that are untypical for melanoma also were included. Among all patients, CNVs were identified in one‐third of samples and contained amplifications of druggable kinases, such as CDK4, ERBB2, and KIT. Considering SNVs and CNVs, 60% of patients with metastases exhibited co‐occurring activations of at least 2 pathways, thus providing a rationale for individualized combination therapies. Unexpectedly, 9% of patients carry potentially protumorigenic germline mutations frequently affecting receptor tyrosine kinases. Remarkably two‐thirds of BRAF/NRAS wild‐type melanomas harbor activating mutations or CNVs in receptor tyrosine kinases.

Conclusions

The results indicate that the integrated analysis of SNVs, CNVs, and germline mutations reveals new druggable targets for combination tumor therapy.

https://ift.tt/2GwdguO

[cancersfakianakis1]

Predominance of triple wild-type and IGF2R mutations in mucosal melanomas

Abstract

Background

Primary mucosal melanoma (MM) is a rare subtype of melanoma that arises from melanocytes in the mucosa. MM has not been well profiled for mutations and its etiology is not well understood, rendering current treatment strategies unsuccessful. Hence, we investigated mutational landscape for MM to understand its etiology and to clarify mutations that are potentially relevant for MM treatment.

Methods

Forty one MM and 48 cutaneous melanoma (CM) tissues were profiled for mutations using targeted deep next-generation sequencing (NGS) for 89 cancer-related genes. A total of 997 mutations within exons were analyzed for their mutational spectrum and prevalence of mutation, and 685 non-synonymous variants were investigated to identify mutations in individual genes and pathways. PD-L1 expression from 21 MM and 18 CM were assessed by immunohistochemistry.

Results

Mutational spectrum analysis revealed a lower frequency of UV-induced DNA damage in MM than in CM (p = 0.001), while tobacco exposure was indicated as a potential etiologic factor for MM. In accordance with low UV damage signatures, MM demonstrated an overall lower number of mutations compared to CM (6.5 mutations/Mb vs 14.8 mutations/Mb, p = 0.001), and less PD-L1 expression (p = 0.003). Compared to CM, which showed frequent mutations in known driver genes (BRAF 50.0%, NRAS 29.2%), MM displayed lower mutation frequencies (BRAF; 12.2%, p < 0.001, NRAS; 17.1%), and was significantly more enriched for triple wild-type (no mutations in BRAF, RAS, or NF1, 70.7% vs 25.0%, p < 0.001), IGF2R mutation (31.7% vs 6.3%, p = 0.002), and KIT mutation (9.8% vs 0%, p = 0.042). Of clinical relevance, presence of DCC mutations was significantly associated with poorer overall survival in MM (log-rank test, p = 0.02). Furthermore, mutational spectrum analysis distinguished primary anorectal MM from CM metastasized to the bowel (spectrum analysis p < 0.001, number of mutations p = 0.002).

Conclusions

These findings demonstrated a potential etiologic factor and driver mutation for MM and strongly suggested that MM initiation or progression involves distinct molecular-mechanisms from CM. This study also identified mutational signatures that are clinically relevant for MM treatment.

https://ift.tt/2qi0chC

[cancersfakianakis1]

The gene mutational discrepancies between primary and paired metastatic colorectal carcinoma detected by next-generation sequencing

Abstract

Purpose

To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method.

Methods

The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing.

Results

Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS.

Conclusion

The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.

https://ift.tt/2PTcdFt