Paired genetic analysis by next-generation sequencing of lung cancer and associated idiopathic pulmonary fibrosis

Kohei Otsubo, Eiji Iwama, Kayo Ijichi, Naoki Kubo, Yasuto Yoneshima, Hiroyuki Inoue, Kentaro Tanaka, Atsushi Osoegawa, Tetsuzo Tagawa, Yoichi Nakanishi, Isamu Okamoto

Research output: Contribution to journalArticlepeer-review

Abstract

The pathogenesis of lung cancer associated with idiopathic pulmonary fibrosis (IPF) has remained largely uncharacterized. To provide insight into this condition, we undertook genomic profiling of IPF-associated lung cancer as well as of adjacent fibrosing lung tissue in surgical specimens. Isolated DNA and RNA from 17 IPF-associated non-small cell lung cancer and 15 paired fibrosing lung tissue specimens were analyzed by next-generation sequencing with a panel that targets 161 cancer-related genes. Somatic genetic alterations were frequently identified in TP53 (n = 6, 35.3%) and PIK3CA (n = 5, 29.4%) genes in tumor samples as well as in EGFR (n = 7, 46.7%), PIK3CA (n = 5, 33.3%), ERBB3 (n = 4, 26.7%), and KDR (n = 4, 26.7%) in IPF samples. Genes related to the RAS-RAF signaling pathway were also frequently altered in tumor (n = 7, 41.2%) and IPF (n = 3, 20.0%) samples. The number of somatic alterations identified in IPF samples was almost as large as that detected in paired tumor samples (81 vs 90, respectively). However, only 6 of the 81 somatic alterations detected in IPF samples overlapped with those in paired tumor samples. The accumulation of somatic mutations was thus apparent in IPF tissue of patients with IPF-associated lung cancer, and the RAS-RAF pathway was implicated in lung tumorigenesis. The finding that somatic alterations were not frequently shared between tumor and corresponding IPF tissue indicates that IPF-associated lung cancer does not develop through the stepwise accumulation of somatic alterations in IPF.

Original languageEnglish
Pages (from-to)2482-2487
Number of pages6
JournalCancer Science
Volume111
Issue number7
DOIs
Publication statusPublished - Jul 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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