TY - JOUR
T1 - Genomic Classification of Cutaneous Melanoma
AU - The Cancer Genome Atlas Network
AU - Akbani, Rehan
AU - Akdemir, Kadir C.
AU - Aksoy, B. Arman
AU - Albert, Monique
AU - Ally, Adrian
AU - Amin, Samirkumar B.
AU - Arachchi, Harindra
AU - Arora, Arshi
AU - Auman, J. Todd
AU - Ayala, Brenda
AU - Baboud, Julien
AU - Balasundaram, Miruna
AU - Balu, Saianand
AU - Barnabas, Nandita
AU - Bartlett, John
AU - Bartlett, Pam
AU - Bristow, Christopher A.
AU - Calderone, Tiffany
AU - Chin, Lynda
AU - Davies, Michael A.
AU - Deribe, Yonathan Lissanu
AU - Genovese, Giannicola
AU - Gershenwald, Jeffrey E.
AU - Ju, Zhenlin
AU - Korkut, Anil
AU - Kwong, Lawrence N.
AU - Lazar, Alexander J.
AU - Lee, Jeffrey E.
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Miller, John Paul
AU - Mills, Gordon B
AU - Muller, Florian
AU - Nezi, Luigi
AU - Prieto, Victor G.
AU - Rai, Kunal
AU - Ross, Merrick I.
AU - Roszik, Jason
AU - Song, Xingzhi
AU - Tsai, Kenneth Y
AU - Tsou, Peiling
AU - Verhaak, Roeland
AU - Wang, Yuling
AU - Watson, Ian Robert
AU - Weinstein, John N.
AU - Woodman, Scott E.
AU - Wu, Chang-Jiun
AU - Wu, Chia Chin
AU - Zhang, Wei
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/6/20
Y1 - 2015/6/20
N2 - Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.
AB - Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.
UR - http://www.scopus.com/inward/record.url?scp=84935009372&partnerID=8YFLogxK
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U2 - 10.1016/j.cell.2015.05.044
DO - 10.1016/j.cell.2015.05.044
M3 - Article
C2 - 26091043
AN - SCOPUS:84935009372
SN - 0092-8674
VL - 161
SP - 1681
EP - 1696
JO - Cell
JF - Cell
IS - 7
ER -