整合基因组学用于在臂水平体细胞拷贝数改变中精准定位生存位点。

Integrated Genomics for Pinpointing Survival Loci within Arm-Level Somatic Copy Number Alterations.

作者信息

Roy David M, Walsh Logan A, Desrichard Alexis, Huse Jason T, Wu Wei, Gao JianJiong, Bose Promita, Lee William, Chan Timothy A

机构信息

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

出版信息

Cancer Cell. 2016 May 9;29(5):737-750. doi: 10.1016/j.ccell.2016.03.025.

DOI:10.1016/j.ccell.2016.03.025

PMID:27165745

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4864611/

Abstract

The identification of driver loci underlying arm-level somatic copy number alterations (SCNAs) in cancer has remained challenging and incomplete. Here, we assess the relative impact and present a detailed landscape of arm-level SCNAs in 10,985 patient samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Furthermore, using chromosome 9p loss in lower grade glioma (LGG) as a model, we employ a unique multi-tiered genomic dissection strategy using 540 patients from three independent LGG datasets to identify genetic loci that govern tumor aggressiveness and poor survival. This comprehensive approach uncovered several 9p loss-specific prognostic markers, validated existing ones, and redefined the impact of CDKN2A loss in LGG.

摘要

在癌症中，识别臂水平体细胞拷贝数改变（SCNAs）背后的驱动基因座一直具有挑战性且不完整。在此，我们评估了其相对影响，并展示了来自癌症基因组图谱（TCGA）的33种癌症类型中10985例患者样本的臂水平SCNAs的详细情况。此外，我们以低级别胶质瘤（LGG）中9号染色体短臂缺失为模型，采用独特的多层次基因组剖析策略，对来自三个独立LGG数据集的540例患者进行研究，以识别控制肿瘤侵袭性和不良生存的基因座。这种综合方法发现了几个9p缺失特异性预后标志物，验证了现有标志物，并重新定义了CDKN2A缺失在LGG中的影响。