title: Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes.
abstract: 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.
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3].
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2].
authors.forename: O Alejandro
authors.initials: OA
authors.lastname: Balbin
authors.affiliation: 1] Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2].
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Shanker
authors.initials: S
authors.lastname: Kalyana-Sundaram
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Pan
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Veeneman
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Malik
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Vats
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Huang
authors.affiliation: Xinjiang Medical University, Xinjiang 830011, China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jing
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Iyer
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
authors.affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Rishindra
authors.initials: R
authors.lastname: Reddy
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Brennan
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Lung Cancer Unit, IRCCS AOU San Martino-IST National Institute for Cancer Research, Genoa 16132, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Truini
authors.affiliation: Department of Pathology, IRCCS AOU San Martino-IST National Institute for Cancer Research, Genoa 16132, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Robinson
authors.affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [4] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling; D050939:Gene Fusion; D000090683:Hippo Signaling Pathway; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009154:Mutation; D020890:Neuregulin-1 / Q000235:genetics* / Q000378:metabolism; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C094131:NRG1 protein, human; D020890:Neuregulin-1; D025542:Neurofibromin 1; C045084:invariant chain; D017346:Protein Serine-Threonine Kinases