Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes

被引：124

作者：

Dhanasekaran, Saravana M. ^{[1
,2
]}

Balbin, O. Alejandro ^{[1
]}

Chen, Guoan ^{[3
]}

Nadal, Ernest ^{[3
]}

Kalyana-Sundaram, Shanker ^{[1
]}

Pan, Jincheng ^{[1
]}

Veeneman, Brendan ^{[1
]}

Cao, Xuhong ^{[1
]}

Malik, Rohit ^{[1
]}

Vats, Pankaj ^{[1
]}

Wang, Rui ^{[1
]}

Huang, Stephanie ^{[1
]}

Zhong, Jinjie ^{[4
]}

Jing, Xiaojun ^{[1
]}

Iyer, Matthew ^{[1
]}

Wu, Yi-Mi ^{[1
]}

Harms, Paul W. ^{[1
,2
,5
]}

Lin, Jules ^{[3
]}

Reddy, Rishindra ^{[3
]}

Brennan, Christine ^{[1
]}

Palanisamy, Nallasivam ^{[1
,2
,6
]}

Chang, Andrew C. ^{[3
]}

Truini, Anna ^{[7
]}

Truini, Mauro ^{[8
]}

Robinson, Dan R. ^{[1
]}

Beer, David G. ^{[3
]}

Chinnaiyan, Arul M. ^{[1
,2
,6
,9
]}

机构：

[1] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

[4] Xinjiang Med Univ, Xinjiang 830011, Peoples R China

[5] Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[7] IRCCS AOU San Martino IST Natl Inst Canc Res, Lung Canc Unit, I-16132 Genoa, Italy

[8] IRCCS AOU San Martino IST Natl Inst Canc Res, Dept Pathol, I-16132 Genoa, Italy

[9] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ADENOID CYSTIC CARCINOMAS; EML4-ALK FUSION GENE; MUCINOUS ADENOCARCINOMA; DIFFERENTIAL GENE; MUTATIONS; IDENTIFICATION; ALK; RET; ACTIVATION; BREAST;

D O I：

10.1038/ncomms6893

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyse 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumours without known driver mutations. In addition, we observe exon-skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations.

引用

页数：12

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