The landscape of somatic copy-number alteration across human cancers

生物 癌变 癌症 体细胞 遗传学 MCL1 癌症研究 基因组 计算生物学 基因 下调和上调
作者
Rameen Beroukhim,Craig H. Mermel,Dale Porter,Wei Guo,Soumya Raychaudhuri,Jerry Donovan,Jordi Barretina,Jesse S. Boehm,Jennifer Dobson,Mitsuyoshi Urashima,Kevin T. Mc Henry,Reid M. Pinchback,Azra H. Ligon,Yoon‐Jae Cho,Leila Haery,Heidi Greulich,Michael Reich,Wendy Winckler,Michael S. Lawrence,Barbara A. Weir
出处
期刊:Nature [Nature Portfolio]
卷期号:463 (7283): 899-905 被引量:3761
标识
DOI:10.1038/nature08822
摘要

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types. Two Articles in this issue add major data sets to the growing picture of the cancer genome. Bignell et al. analysed a large number of homozygous gene deletions in a collection of 746 publicly available cancer cell lines. Combined with information about hemizygous deletions of the same genes, the data suggest that many deletions found in cancer reflect the position of a gene at a fragile site in the genome, rather than as a recessive cancer gene whose loss confers a selective growth advantage. Beroukhim et al. present the largest data set to date on somatic copy-number variations across more than 3,000 specimens of human primary cancers. Many alterations are shared between multiple tumour types. Functional experiments demonstrate an oncogenic role for the apoptosis genes MCL1 and BCL2L1 that are associated with amplifications found in many cancers. One way of discovering genes with key roles in cancer development is to identify genomic regions that are frequently altered in human cancers. Here, high-resolution analyses of somatic copy-number alterations (SCNAs) in numerous cancer specimens provide an overview of regions of focal SCNA that are altered at significant frequency across several cancer types. An oncogenic function is also found for the anti-apoptosis genes MCL1 and BCL2L1, which reside in amplified genome regions in many cancers.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
小柒完成签到 ,获得积分10
1秒前
聪慧芷巧发布了新的文献求助10
2秒前
3秒前
7秒前
蓝意完成签到,获得积分0
8秒前
xiaohongmao完成签到,获得积分10
13秒前
16秒前
qweerrtt完成签到,获得积分10
23秒前
23秒前
与共发布了新的文献求助10
24秒前
carly完成签到 ,获得积分10
25秒前
颢懿完成签到 ,获得积分10
28秒前
量子星尘发布了新的文献求助10
29秒前
31秒前
ljc完成签到 ,获得积分10
32秒前
Java完成签到,获得积分10
36秒前
38秒前
鲤鱼安青完成签到 ,获得积分10
40秒前
40秒前
dollarpuff完成签到 ,获得积分10
43秒前
43秒前
mmmmmMM完成签到,获得积分10
50秒前
luckweb完成签到,获得积分10
56秒前
猫的毛完成签到 ,获得积分10
57秒前
nicky完成签到 ,获得积分10
58秒前
麦子完成签到 ,获得积分10
59秒前
59秒前
Wilson完成签到 ,获得积分10
1分钟前
luckweb发布了新的文献求助10
1分钟前
1分钟前
1分钟前
1分钟前
传奇3应助wujiwuhui采纳,获得10
1分钟前
开心寄松完成签到,获得积分10
1分钟前
北宫完成签到 ,获得积分10
1分钟前
wansida完成签到,获得积分10
1分钟前
QXS完成签到 ,获得积分10
1分钟前
1分钟前
菠萝完成签到 ,获得积分10
1分钟前
领导范儿应助Villanellel采纳,获得10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022