Robertson A Gordon, Shih Juliann, Yau Christina, Gibb Ewan A, Oba Junna, Mungall Karen L, Hess Julian M, Uzunangelov Vladislav, Walter Vonn, Danilova Ludmila, Lichtenberg Tara M, Kucherlapati Melanie, Kimes Patrick K, Tang Ming, Penson Alexander, Babur Ozgun, Akbani Rehan, Bristow Christopher A, Hoadley Katherine A, Iype Lisa, Chang Matthew T, Cherniack Andrew D, Benz Christopher, Mills Gordon B, Verhaak Roel G W, Griewank Klaus G, Felau Ina, Zenklusen Jean C, Gershenwald Jeffrey E, Schoenfield Lynn, Lazar Alexander J, Abdel-Rahman Mohamed H, Roman-Roman Sergio, Stern Marc-Henri, Cebulla Colleen M, Williams Michelle D, Jager Martine J, Coupland Sarah E, Esmaeli Bita, Kandoth Cyriac, Woodman Scott E
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Cancer Cell. 2017 Aug 14;32(2):204-220.e15. doi: 10.1016/j.ccell.2017.07.003.
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.
对80例葡萄膜黑色素瘤（UM）进行的综合多平台分析确定了四种分子上不同且与临床相关的亚型：两种与预后不良的3号染色体单体（M3）相关，两种与预后较好的3号染色体二体（D3）相关。我们发现BAP1缺失发生在M3之后，并且与一种不同于D3-UM的整体DNA甲基化状态相关。预后不良的M3-UM可分为具有不同基因组畸变、转录特征和临床结果的亚组。我们报告了功能改变的SRSF2突变。在D3-UM中，EIF1AX和SRSF2/SF3B1突变的肿瘤具有不同的体细胞拷贝数改变和DNA甲基化谱，这为深入了解这些低风险与中风险临床突变亚型的生物学特性提供了线索。
