Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.,Cancer Cell

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.
Cancer Cell ( IF 48.8 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.ccell.2017.07.003
A Gordon Robertson ₁ , Juliann Shih ₂ , Christina Yau ₃ , Ewan A Gibb ₁ , Junna Oba ₄ , Karen L Mungall ₁ , Julian M Hess ₅ , Vladislav Uzunangelov ₆ , Vonn Walter ₇ , Ludmila Danilova ₈ , Tara M Lichtenberg ₉ , Melanie Kucherlapati ₁₀ , Patrick K Kimes ₁₁ , Ming Tang ₁₂ , Alexander Penson ₁₃ , Ozgun Babur ₁₄ , Rehan Akbani ₁₅ , Christopher A Bristow ₁₆ , Katherine A Hoadley ₁₇ , Lisa Iype ₁₈ , Matthew T Chang ₁₉ , , Andrew D Cherniack ₂ , Christopher Benz ₃ , Gordon B Mills ₂₀ , Roel G W Verhaak ₂₁ , Klaus G Griewank ₂₂ , Ina Felau ₂₃ , Jean C Zenklusen ₂₃ , Jeffrey E Gershenwald ₂₄ , Lynn Schoenfield ₂₅ , Alexander J Lazar ₂₆ , Mohamed H Abdel-Rahman ₂₇ , Sergio Roman-Roman ₂₈ , Marc-Henri Stern ₂₈ , Colleen M Cebulla ₂₉ , Michelle D Williams ₂₆ , Martine J Jager ₃₀ , Sarah E Coupland ₃₁ , Bita Esmaeli ₃₂ , Cyriac Kandoth ₃₃ , Scott E Woodman ₃₄

Affiliation

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.
Buck Institute for Research on Aging, Novato, CA 94945, USA.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, CA 95064, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Public Health Sciences, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA.
The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Human Oncology and Pathogenesis Program, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Molecular and Medical Genetics, Computational Biology, Oregon Health and Science University, Portland, OR 97239, USA.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Institute for Applied Cancer Science, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Institute for Systems Biology, Seattle, WA 98109, USA.
Human Oncology and Pathogenesis Program, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Departments of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94122, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Dermatology, University Hospital Essen, 45157 Essen, Germany.
Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA.
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Pathology, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Department of Pathology, Dermatology and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Departments of Ophthalmology and Internal Medicine, Division of Human Genetics, The Ohio State University, Columbus, OH 43210, USA.
Department of Translational Research, Institut Curie, PSL Research University, Paris 75248, France.
Havener Eye Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43212, USA.
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Molecular & Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool L7 8TX, UK; Department of Cellular Pathology, Royal Liverpool University Hospital, Liverpool, L69 3GA, UK.
Orbital Oncology & Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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.

中文翻译：

综合分析确定葡萄膜黑色素瘤的四个分子和临床亚群。

对 80 个葡萄膜黑色素瘤 (UM) 的综合多平台分析确定了四种分子不同的、临床相关的亚型：两种与预后不良的 3 单体 (M3) 相关，两种与预后较好的 3 单体 (D3) 相关。我们表明 BAP1 丢失跟随 M3 发生，并与不同于 D3-UM 的全局 DNA 甲基化状态相关。预后不良的 M3-UM 分为具有不同基因组畸变、转录特征和临床结果的亚组。我们报告功能改变 SRSF2 突变。在 D3-UM 中，EIF1AX 和 SRSF2/SF3B1 突变肿瘤具有不同的体细胞拷贝数改变和 DNA 甲基化谱，提供了对这些低风险和中等风险临床突变亚型的生物学的深入了解。

更新日期：2017-08-14

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11