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

• Published in: Nature communications Vol. 6; no. 1; p. 10131
• Main Authors: Wu, Kui, Zhang, Xin, Li, Fuqiang, Xiao, Dakai, Hou, Yong, Zhu, Shida, Liu, Dongbing, Ye, Xiaofei, Ye, Mingzhi, Yang, Jie, Shao, Libin, Pan, Hui, Lu, Na, Yu, Yuan, Liu, Liping, Li, Jin, Huang, Liyan, Tang, Hailing, Deng, Qiuhua, Zheng, Yue, Peng, Lihua, Liu, Geng, Gu, Xia, He, Ping, Gu, Yingying, Lin, Weixuan, He, Huiming, Xie, Guoyun, Liang, Han, An, Na, Wang, Hui, Teixeira, Manuel, Vieira, Joana, Liang, Wenhua, Zhao, Xin, Peng, Zhiyu, Mu, Feng, Zhang, Xiuqing, Xu, Xun, Yang, Huanming, Kristiansen, Karsten, Wang, Jian, Zhong, Nanshan, Wang, Jun, Pan-Hammarström, Qiang, He, Jianxing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.12.2015; Nature Publishing Group
• Subjects: 631/67/1612; 631/67/322; 631/67/68; 692/53/2422; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Asians - genetics; Cytoskeleton; Cytoskeleton - genetics; Cytoskeleton - metabolism; Female; Genomes; Genomics; Hospitals; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphatic Metastasis - genetics; Lymphatic system; Male; Medicin och hälsovetenskap; Metastasis; Middle Aged; multidisciplinary; Mutation; Pathogenesis; Research centers; Respiratory diseases; Science; Science (multidisciplinary); Thoracic surgery; Tumors; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10131

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. Despite lung adenocarcinoma having a high global mortality, the genetic mutations present in Asian patients are uncharacterized. Here the authors use genomic and transcriptomic analysis to identify thirteen significantly affected genes, including RHPN2 , GLI3 , MRC2 , TP53 and IQGAP3 .