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Nat Commun. 2015 Dec 9;6:10131. doi: 10.1038/ncomms10131.

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.

Wu K1,2,3,4,5, Zhang X2,3,4, Li F1, Xiao D2,3,6, Hou Y1,5, Zhu S1,5, Liu D1, Ye X1,7, Ye M1,8, Yang J1, Shao L1, Pan H2,3,6, Lu N1, Yu Y1, Liu L2,3,6, Li J2,3,6, Huang L2,3, Tang H2,3, Deng Q2,3,6, Zheng Y1, Peng L1, Liu G1, Gu X9, He P9, Gu Y3,9, Lin W6, He H6, Xie G1, Liang H1, An N1, Wang H1, Teixeira M10, Vieira J10, Liang W2,3,4, Zhao X1, Peng Z1,8, Mu F1,11, Zhang X1,8, Xu X1, Yang H1,12, Kristiansen K1,2, Wang J1,12, Zhong N3,4, Wang J1,5, Pan-Hammarström Q1,7, He J2,3,4.

Author information

1
BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
2
Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
3
Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.
4
National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
5
Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
6
Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
7
Department of Laboratory of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
8
Guangzhou Key Laboratory of Cancer Trans-Omics Research, BGI-Guangzhou, Guangzhou 510006, China.
9
Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
10
Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal.
11
BGI-Wuhan, Wuhan 430075, China.
12
James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou 310058, China.

Abstract

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.

PMID:
26647728
PMCID:
PMC4682110
DOI:
10.1038/ncomms10131
[Indexed for MEDLINE]
Free PMC Article

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