Identification and Characterization of Cancer Mutations in Japanese Lung Adenocarcinoma Without Sequencing of Normal Tissue Counterparts

PLoS One. 2013 Sep 12;8(9):e73484. doi: 10.1371/journal.pone.0073484. eCollection 2013.

Abstract

We analyzed whole-exome sequencing data from 97 Japanese lung adenocarcinoma patients and identified several putative cancer-related genes and pathways. Particularly, we observed that cancer-related mutation patterns were significantly different between different ethnic groups. As previously reported, mutations in the EGFR gene were characteristic to Japanese, while those in the KRAS gene were more frequent in Caucasians. Furthermore, during the course of this analysis, we found that cancer-specific somatic mutations can be detected without sequencing normal tissue counterparts. 64% of the germline variants could be excluded using a total of 217 external Japanese exome datasets. We also show that a similar approach may be used for other three ethnic groups, although the discriminative power depends on the ethnic group. We demonstrate that the ATM gene and the PAPPA2 gene could be identified as cancer prognosis related genes. By bypassing the sequencing of normal tissue counterparts, this approach provides a useful means of not only reducing the time and cost of sequencing but also analyzing archive samples, for which normal tissue counterparts are not available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • Asian Continental Ancestry Group / genetics
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Mutation / genetics

Grant support

This work was supported by JSPS KAKENHI Grant number 24300345. This work was also supported by MEXT KAKENHI Grant Number 221S0002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.