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

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  • Saravana M. Dhanasekaran

    (Michigan Center for Translational Pathology, University of Michigan Medical School
    University of Michigan Medical School)

  • O Alejandro Balbin

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Guoan Chen

    (Thoracic Surgery, University of Michigan Medical School)

  • Ernest Nadal

    (Thoracic Surgery, University of Michigan Medical School)

  • Shanker Kalyana-Sundaram

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Jincheng Pan

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Brendan Veeneman

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Xuhong Cao

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Rohit Malik

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Pankaj Vats

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Rui Wang

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Stephanie Huang

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Jinjie Zhong

    (Xinjiang Medical University)

  • Xiaojun Jing

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Matthew Iyer

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Yi-Mi Wu

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Paul W. Harms

    (Michigan Center for Translational Pathology, University of Michigan Medical School
    University of Michigan Medical School
    University of Michigan Medical School)

  • Jules Lin

    (Thoracic Surgery, University of Michigan Medical School)

  • Rishindra Reddy

    (Thoracic Surgery, University of Michigan Medical School)

  • Christine Brennan

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • Nallasivam Palanisamy

    (Michigan Center for Translational Pathology, University of Michigan Medical School
    University of Michigan Medical School
    Comprehensive Cancer Center, University of Michigan Medical School)

  • Andrew C. Chang

    (Thoracic Surgery, University of Michigan Medical School)

  • Anna Truini

    (Lung Cancer Unit, IRCCS AOU San Martino-IST National Institute for Cancer Research)

  • Mauro Truini

    (IRCCS AOU San Martino-IST National Institute for Cancer Research)

  • Dan R. Robinson

    (Michigan Center for Translational Pathology, University of Michigan Medical School)

  • David G. Beer

    (Thoracic Surgery, University of Michigan Medical School)

  • Arul M. Chinnaiyan

    (Michigan Center for Translational Pathology, University of Michigan Medical School
    University of Michigan Medical School
    Comprehensive Cancer Center, University of Michigan Medical School
    Howard Hughes Medical Institute, University of Michigan Medical School)

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.

Suggested Citation

  • 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 H, 2014. "Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6893
    DOI: 10.1038/ncomms6893
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