Beyond BRAFV600: Clinical mutation panel testing by next-generation sequencing in advanced melanoma

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

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had > 1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600 and NRAS mutations. Melanomas with BRAFNon-V600 mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600 and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalJournal of Investigative Dermatology
Volume135
Issue number2
DOIs
StatePublished - Feb 13 2015
Externally publishedYes

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Tumors
Melanoma
Mutation
Testing
Genes
Neoplasms
Skin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Siroy, A. E., Boland, G. M., Milton, D. R., Roszik, J., Frankian, S., Malke, J., ... Davies, M. A. (2015). Beyond BRAFV600: Clinical mutation panel testing by next-generation sequencing in advanced melanoma. Journal of Investigative Dermatology, 135(2), 508-515. https://doi.org/10.1038/jid.2014.366

Beyond BRAFV600 : Clinical mutation panel testing by next-generation sequencing in advanced melanoma. / Siroy, Alan E.; Boland, Genevieve M.; Milton, Denái R.; Roszik, Jason; Frankian, Silva; Malke, Jared; Haydu, Lauren; Prieto, Victor G.; Tetzlaff, Michael; Ivan, Doina; Wang, Wei Lien; Torres-Cabala, Carlos; Curry, Jonathan; Roy-Chowdhuri, Sinchita; Broaddus, Russell; Rashid, Asif; Stewart, John; Gershenwald, Jeffrey E.; Amaria, Rodabe N.; Patel, Sapna P.; Papadopoulos, Nicholas E.; Bedikian, Agop; Hwu, Wen Jen; Hwu, Patrick; Diab, Adi; Woodman, Scott E.; Aldape, Kenneth D.; Luthra, Rajyalakshmi; Patel, Keyur P.; Shaw, Kenna R.; Mills, Gordon; Mendelsohn, John; Meric-Bernstam, Funda; Kim, Kevin B.; Routbort, Mark J.; Lazar, Alexander J.; Davies, Michael A.

In: Journal of Investigative Dermatology, Vol. 135, No. 2, 13.02.2015, p. 508-515.

Research output: Contribution to journalArticle

Siroy, AE, Boland, GM, Milton, DR, Roszik, J, Frankian, S, Malke, J, Haydu, L, Prieto, VG, Tetzlaff, M, Ivan, D, Wang, WL, Torres-Cabala, C, Curry, J, Roy-Chowdhuri, S, Broaddus, R, Rashid, A, Stewart, J, Gershenwald, JE, Amaria, RN, Patel, SP, Papadopoulos, NE, Bedikian, A, Hwu, WJ, Hwu, P, Diab, A, Woodman, SE, Aldape, KD, Luthra, R, Patel, KP, Shaw, KR, Mills, G, Mendelsohn, J, Meric-Bernstam, F, Kim, KB, Routbort, MJ, Lazar, AJ & Davies, MA 2015, 'Beyond BRAFV600: Clinical mutation panel testing by next-generation sequencing in advanced melanoma', Journal of Investigative Dermatology, vol. 135, no. 2, pp. 508-515. https://doi.org/10.1038/jid.2014.366
Siroy, Alan E. ; Boland, Genevieve M. ; Milton, Denái R. ; Roszik, Jason ; Frankian, Silva ; Malke, Jared ; Haydu, Lauren ; Prieto, Victor G. ; Tetzlaff, Michael ; Ivan, Doina ; Wang, Wei Lien ; Torres-Cabala, Carlos ; Curry, Jonathan ; Roy-Chowdhuri, Sinchita ; Broaddus, Russell ; Rashid, Asif ; Stewart, John ; Gershenwald, Jeffrey E. ; Amaria, Rodabe N. ; Patel, Sapna P. ; Papadopoulos, Nicholas E. ; Bedikian, Agop ; Hwu, Wen Jen ; Hwu, Patrick ; Diab, Adi ; Woodman, Scott E. ; Aldape, Kenneth D. ; Luthra, Rajyalakshmi ; Patel, Keyur P. ; Shaw, Kenna R. ; Mills, Gordon ; Mendelsohn, John ; Meric-Bernstam, Funda ; Kim, Kevin B. ; Routbort, Mark J. ; Lazar, Alexander J. ; Davies, Michael A. / Beyond BRAFV600 : Clinical mutation panel testing by next-generation sequencing in advanced melanoma. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 2. pp. 508-515.
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AU - Roszik, Jason

AU - Frankian, Silva

AU - Malke, Jared

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AU - Bedikian, Agop

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AU - Hwu, Patrick

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AU - Aldape, Kenneth D.

AU - Luthra, Rajyalakshmi

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AU - Shaw, Kenna R.

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AU - Kim, Kevin B.

AU - Routbort, Mark J.

AU - Lazar, Alexander J.

AU - Davies, Michael A.

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