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

Saravana M. Dhanasekaran  O Alejandro Balbin  Guoan Chen  Ernest Nadal  Shanker Kalyana-Sundaram  Jincheng Pan  Brendan Veeneman  Xuhong Cao  Rohit Malik  Pankaj Vats  Rui Wang Stephanie Huang  Jinjie Zhong  Xiaojun Jing  Matthew Iyer  Yi-Mi Wu  Paul W. Harms  Jules Lin Rishindra Reddy  Christine Brennan  Nallasivam Palanisamy  Andrew C. Chang  Anna Truini Mauro Truini  Dan R. Robinson  David G. Beer  Arul M. Chinnaiyan

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.

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