Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis

Yuta Takahashi, Kazuhiko Shien, Shuta Tomida, Shinsuke Oda, Takehiro Matsubara, Hiroki Sato, Ken Suzawa, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Takahiro Yoshioka, Hidejiro Torigoe, Hiromasa Yamamoto, Junichi Sou, Shinichi Toyooka

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer-related oncogenes using next-generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.

Original languageEnglish
Pages (from-to)3634-3642
Number of pages9
JournalCancer Science
Issue number11
Publication statusPublished - Nov 2018


  • classification
  • clonality
  • gene mutation
  • multiple lung cancer
  • next-generation sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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