Beyond BRAF V600 : Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma

Siroy, Alan; Boland, Genevieve M.; Milton, Denái R.; Roszik, Jason; Frankian, Silva; Malke, Jared; Haydu, Lauren E.; Prieto, Víctor G.; Tetzlaff, Michael T.; Ivan, Doina; Wang, Wei Lien; Torres‐Cabala, Carlos A.; Roy‐Chowdhuri, Sinchita; Broaddus, Russell R.; Rashid, Asif; Stewart, John; Gershenwald, Jeffrey E.; Amaria, Rodabe N.; Patel, Sapna; Papadopoulos, Nicholas E.; Bedikian, Agop Y.; Hwu, Wen Jen; Hwu, Patrick; Diab, Adi; Woodman, Scott E.; Aldape, Kenneth; Luthra, Rajyalakshmi; Patel, Keyur P.; Shaw, Kenna; Mills, Gordon B.; Mendelsohn, John; Meric‐Bernstam, Funda; Kim, Kevin B.; Routbort, Mark J.; Lazar, Alexander J.; Davies, Michael A.

doi:10.1038/jid.2014.366

Cited by 131 publications

(130 citation statements)

References 37 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…Many studies have revealed that the BRAF mutation is associated with younger age, nodular or superficial spreading histological type, tumour location on the trunk and intermittent sun exposure (5,15,17,20). Also, a study by Hughahl et al (22) revealed the association between higher rates of BRAF V600 immunohistochemistry expression and increased tumour thickness, presence of ulceration and higher rates of mitosis.…”

Section: Discussionmentioning

confidence: 99%

Braf v600 mutation profile of metastatic melanoma in the thrace region of turkey

Can¹,

Taştekin²,

Yalta³

et al. 2018

TJPATH

View full text Add to dashboard Cite

Objective: BRAF is the most common mutation in melanoma. The most common subtype is BRAF V600E, followed by V600K. Initially, the authors aimed to investigate whether clinicopathological features of melanoma are associated with BRAF mutations. We then aimed to present the relationships between the clinicopathological features and the mutated subtype (V600E vs V600K). Material and Method:61 patients with metastatic malignant melanoma (affecting the lymph node or other distant sites) were selected. Patient data regarding age at the time of diagnosis, sex, metastatic site (lymph node, distant metastasis or both) and primary tumour site were obtained from the hospital's database. Tissue samples containing at least 30% tumour cells were isolated from the specimens of 61 patients (24 samples from primary tumours and 37 from metastatic foci) for BRAF analysis. Comparisons between the BRAF V600 mutation and clinicopathological and histopathological features were performed.Results: BRAF V600 mutation was detected in 34 (55.7%) patients. The subtype was BRAF V600E in 22 (64.7%) patients, BRAF V600K in 11(32.4%) patients and BRAF V600R in 1(2.9%) patient. The crucial results of the present study may be summarized as follows: i) BRAF V600 mutation was more common in older patients and tumors with BRAF V600 mutation revealed necrosis and LVI more commonly than wild-type tumors, ii) BRAF V600K mutation was more common in older patients and BRAF V600K mutated tumors exhibited ulceration more commonly than tumors with BRAF V600E mutation (close to significant). Conclusion:The BRAF V600 mutation may have interactions with prognostic clinicoptahological features of melanoma including necrosis and lymphovascular invasion. V600K mutation may be more common than expected and may have different associations with properties of the tumor such as tumor ulceration and patient age. Investigation of the mutated subtype of the BRAF gene may therefore reveal more detailed data about the management of melanoma and may also prevent missing of candidates for BRAF inhibitor therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Braf v600 mutation profile of metastatic melanoma in the thrace region of turkey

Can¹,

Taştekin²,

Yalta³

et al. 2018

TJPATH

View full text Add to dashboard Cite

show abstract

“…17 Approximately 40-50 % of cutaneous melanomas have a constitutive activating mutation in BRAF V600 . 18,19 Selective small molecule inhibitors, vemurafenib and dabrafenib, are available and have been shown to postpone disease progression in patients with metastatic melanoma and an identified BRAF V600 mutation. 20 A phase 3 randomized controlled study comparing vemurafenib to standard chemotherapy (dacarbazine) demonstrated a significant survival advantage at 6 months (84 vs. 64 %) with response rates of 48 versus 5 %.…”

Section: Acquired/somatic Mutationsmentioning

confidence: 99%

Melanoma: Advances in Targeted Therapy and Molecular Markers

DePeralta

Boland

2015

Ann Surg Oncol

Self Cite

View full text Add to dashboard Cite

Germ-line and somatic mutations are common in melanoma and provide prognostic information that can now be harnessed to provide a more personalized approach to cancer treatment. BRAF mutation at the V600 position is the most commonly identified mutation in patients with melanoma. Treatment with targeted inhibitors in patients with BRAF-mutant melanoma has afforded dramatic responses in about half of selected patients. Unfortunately, disease control is not durable and recurrences are common. We predict an increasing role for the surgeon in the multidisciplinary treatment of patients with metastatic disease, as well as a role for molecular profiling in patients with high-risk early stage disease. Further, we are only beginning to understand the prognostic significance of various gene mutations in patients with melanoma.

show abstract

“…Limited small individual trials showed that BRAF K601E and L597Q are at least partially sensitive to trametinib (MEK inhibitor), with 3 of 5 treated patients showing objective clinical and radiological response with a very manageable toxicity profile [51]. Similarly, another study including 45 patients with advanced/metastatic BRAF V600R mutant melanoma showed an overall response rate of 50% for the whole population, with a progression-free survival of 5.5 months [52].…”

Section: -16 Days >Q30mentioning

confidence: 99%

“…Although promising for BRAF V600E and K, there are very limited findings for BRAF inhibitors in melanomas harboring non-BRAF V600E mutations, which include BRAFV600R, BRAFV601K, and BRAF L597K [51,52]. Limited small individual trials showed that BRAF K601E and L597Q are at least partially sensitive to trametinib (MEK inhibitor), with 3 of 5 treated patients showing objective clinical and radiological response with a very manageable toxicity profile [51].…”

Section: -16 Days >Q30mentioning

confidence: 99%

The history of dermatology, venereology and dermatopathology in different countries - China

Zhang¹,

Chen²,

Zhang³

et al. 2016

Glob Dermatol

View full text Add to dashboard Cite

Volume 3(4): [352][353][354][355][356][357][358] hybridization (FISH), comparative genomic hybridization and SNP array (CGH+SNP) array, and gene expression signature (quantitative reverse transcriptase PCR). Platforms for therapeutic guidance include Sanger sequencing, matrix-associated laser di-ionization time of flight mass spectrometry (MALDITOF-MS), and high-throughput targeted next-generation sequencing (NGS). Each of these platform categories is discussed below. Fluorescence in situ hybridizationConventional cytogenetics and CGH paved the way for FISH in dermatopathology. The initial data published by Bastian et al. in 2002 showed recurrent genomic aberrations in melanomas involving chromosomes 9, 10, 7, and 6, in contrast to most Spitz nevi, which do not show aberrations [3]. The following years witnessed a plethora of publications addressing the application of FISH and its diagnostic and prognostic value in melanocytic lesions.FISH uses fluorescent-labeled probes targeting specific genomic areas of interest. Hybridization of these probes is performed on baked IntroductionSince the sequencing of nearly the entire human genome was first accomplished in 2003 the world of molecular pathology has experienced an exponential evolution [1]. This process evolved from karyotyping (in which whole chromosomes are discernible) to fluorescence in situ hybridization and comparative genomic hybridization (CGH, with which specific megabase regions are visualized), array-based CGH (aCGH), examining hundreds of base pairs and identifying singlenucleotide polymorphisms (SNP), and next-generation sequencing (providing single base pair resolution) [1]. Whole genome nextgeneration sequencing remains a cost-prohibitive method for many investigators, although considerable effort has been made to lower its cost for better incorporation into clinical practice. With the advent of newer technologies the cost of aCGH decreased recent years and the resolution of genome mapping increased [2]. A similar cost reduction has been seen in targeted next-generation sequencing, which has gained tremendous popularity and become the sine qua non for standard testing in personalized medicine centers.Understanding the specific needs of the patient population in each practice and tailoring the different available platforms in that regard, remains the most important point that needs to be taken in consideration when implementing next-generation sequencing techniques. In this review, we will focus on clinical platforms that have shown promising results in diagnosis, prognosis, and theranostics in the clinical practice in dermatopathology. Data generated by these methods will enable pathologists and clinicians to better understand the numerous challenging cases and to design treatment plans customized to the patient's specific tumor. We will not discuss available techniques that are currently limited to research use (whole-genome sequencing, non-targeted RNA sequencing).From a practical standpoint, the different molecular platforms in clinical dermato...

show abstract

Beyond BRAF V600 : Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma

Cited by 131 publications

References 37 publications

Braf v600 mutation profile of metastatic melanoma in the thrace region of turkey

Braf v600 mutation profile of metastatic melanoma in the thrace region of turkey

Melanoma: Advances in Targeted Therapy and Molecular Markers

The history of dermatology, venereology and dermatopathology in different countries - China

Contact Info

Product

Resources

About