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Carcinogenesis. 2015 Jun;36(6):616-21. doi: 10.1093/carcin/bgv026. Epub 2015 Apr 11.

Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing.

Author information

  • 1Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
  • 2Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo 104-0045, Japan.
  • 3Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
  • 4Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo 104-0045, Japan.
  • 5Pathology Division and.
  • 6Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
  • 7Department of Neuro-Oncology/Neurosurgery, International Medical Center, Saitama Medical University, Saitama 350-1298, Japan.
  • 8Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
  • 9Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA.
  • 10Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • 11Bioinfomatics Group, Research and Development Center, Solution Division 4, Hitachi Government and Public Corporation System Engineering Ltd, Tokyo 135-8633, Japan.
  • 12Division of Genetics, National Cancer Center Research Institute, Tokyo 104-0045, Japan and.
  • 13Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Cancer Genome Biology Group, Institute of Predictive and Personalized Medicine of Cancer, 08916 Barcelona, Spain jyokota@ncc.go.jp.

Abstract

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Only 15% of SCLC patients survive beyond 2 years after diagnosis. Therefore, for the improvement of patients' outcome in this disease, it is necessary to identify genetic alterations applicable as therapeutic targets in SCLC cells. The purpose of this study is the identification of genes frequently mutated and expressed in SCLCs that will be targetable for therapy of SCLC patients. Exome sequencing was performed in 28 primary tumors and 16 metastatic tumors from 38 patients with SCLCs. Expression of mutant alleles was verified in 19 cases by RNA sequencing. TP53, RB1 and PTEN were identified as being significantly mutated genes. Additional 36 genes were identified as being frequently (≥10%) mutated in SCLCs by combining the results of this study and two recent studies. Mutated alleles were expressed in 8 of the 36 genes, TMEM132D, SPTA1, VPS13B, CSMD2, ANK2, ASTN1, ASPM and FBN3. In particular, the TMEM132D, SPTA1 and VPS13B genes were commonly mutated in both early and late stage tumors, primary tumors and metastases, and tumors before and after chemotherapy, as in the case of the TP53 and RB1 genes. Therefore, in addition to TP53, RB1 and PTEN, TMEM132D, SPTA1 and VPS13B could be also involved in SCLC development, with the products from their mutated alleles being potential therapeutic targets in SCLC patients.

© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PMID:
25863124
[PubMed - indexed for MEDLINE]
PMCID:
PMC4462675
[Available on 2016-06-01]
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