清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Proteogenomics connects somatic mutations to signalling in breast cancer

蛋白质基因组学 生物 体细胞 乳腺癌 癌症研究 癌症 信号 种系突变 遗传学 计算生物学 基因 突变 基因组 基因组学 细胞生物学
作者
Philipp Mertins,D.R. Mani,Kelly V. Ruggles,Michael A. Gillette,Karl R. Clauser,Pei Wang,Xianlong Wang,Jana Qiao,Song Cao,Francesca Petralia,Emily Kawaler,Filip Mundt,Karsten Krug,Zhidong Tu,Jonathan T. Lei,Michael L. Gatza,Matthew D. Wilkerson,Charles M. Perou,Venkata Yellapantula,Kuan-lin Huang
出处
期刊:Nature [Nature Portfolio]
卷期号:534 (7605): 55-62 被引量:1550
标识
DOI:10.1038/nature18003
摘要

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets. Quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of genomically annotated human breast cancer samples elucidates functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies potential therapeutic targets. This large-scale collaborative study describes quantitative-mass spectrometry-based proteomic and phosphoproteomic analyses of 105 breast cancer samples from The Cancer Genome Atlas (TCGA), representing the four principal mRNA-defined breast cancer intrinsic subtypes. The result is a high-quality proteomic resource for human breast cancer investigation, achieved using technologies and analytical approaches that illuminate the connections between genome and proteome. The data narrow candidate nominations for driver genes within large deletions and amplified regions, and identify potential therapeutic targets.
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
18秒前
Able完成签到,获得积分10
19秒前
我是笨蛋完成签到 ,获得积分10
22秒前
ceeray23发布了新的文献求助20
24秒前
Owen应助董可以采纳,获得10
36秒前
酷酷妙梦完成签到,获得积分10
41秒前
科研通AI2S应助彦嘉采纳,获得10
1分钟前
小二郎应助科研通管家采纳,获得10
1分钟前
hhh2018687完成签到,获得积分10
1分钟前
科研通AI2S应助ceeray23采纳,获得20
1分钟前
忘忧Aquarius完成签到,获得积分10
1分钟前
wujiwuhui完成签到 ,获得积分10
1分钟前
Lny发布了新的文献求助30
2分钟前
sh1ro完成签到,获得积分10
2分钟前
luang应助ceeray23采纳,获得40
2分钟前
2分钟前
ww完成签到,获得积分10
2分钟前
斯文败类应助ceeray23采纳,获得20
3分钟前
机智秋莲发布了新的文献求助20
3分钟前
ChatGPT完成签到,获得积分10
3分钟前
所所应助科研通管家采纳,获得10
3分钟前
3分钟前
3分钟前
ceeray23发布了新的文献求助20
3分钟前
海阔天空完成签到 ,获得积分10
3分钟前
zys发布了新的文献求助10
4分钟前
ffdhdh应助LYZSh采纳,获得10
4分钟前
4分钟前
机智秋莲完成签到,获得积分20
5分钟前
欣欣子完成签到 ,获得积分10
5分钟前
apt完成签到 ,获得积分10
5分钟前
科研通AI2S应助科研通管家采纳,获得10
5分钟前
6分钟前
董可以发布了新的文献求助10
6分钟前
Orange应助董可以采纳,获得10
6分钟前
飞翔的企鹅完成签到,获得积分10
6分钟前
7分钟前
董可以发布了新的文献求助10
7分钟前
LYZSh发布了新的文献求助10
7分钟前
彭于晏应助董可以采纳,获得10
7分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3990543
求助须知:如何正确求助?哪些是违规求助? 3532220
关于积分的说明 11256532
捐赠科研通 3271057
什么是DOI,文献DOI怎么找? 1805207
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234