title: Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.
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.
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.|Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Kui
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Dakai
authors.initials: D
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Shida
authors.initials: S
authors.lastname: Zhu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Dongbing
authors.initials: D
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Laboratory of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ye
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Guangzhou Key Laboratory of Cancer Trans-Omics Research, BGI-Guangzhou, Guangzhou 510006, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Ye
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Peng
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Weixuan
authors.initials: W
authors.lastname: Lin
authors.affiliation: Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: He
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Guoyun
authors.initials: G
authors.lastname: Xie
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Na
authors.initials: N
authors.lastname: An
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Teixeira
authors.affiliation: Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Vieira
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Guangzhou Key Laboratory of Cancer Trans-Omics Research, BGI-Guangzhou, Guangzhou 510006, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|BGI-Wuhan, Wuhan 430075, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Mu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Guangzhou Key Laboratory of Cancer Trans-Omics Research, BGI-Guangzhou, Guangzhou 510006, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.|Department of Laboratory of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.|Guangzhou Institute of Respiratory Disease &State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.|National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation