Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer

PLoS Genet. 2016 Apr 19;12(4):e1005895. doi: 10.1371/journal.pgen.1005895. eCollection 2016 Apr.

Abstract

Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Small Cell / genetics*
  • DNA Copy Number Variations
  • DNA Damage
  • Female
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Oncogene Proteins / genetics*
  • Serine-Arginine Splicing Factors / genetics*

Substances

  • Oncogene Proteins
  • SRSF1 protein, human
  • Serine-Arginine Splicing Factors

Grant support

This study was supported by MedImmune/AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.