Paired genetic analysis by next‐generation sequencing of lung cancer and associated idiopathic pulmonary fibrosis. Issue 7 (10th June 2020)

• Record Type: Journal Article
• Authors: Otsubo, Kohei; Iwama, Eiji; Ijichi, Kayo; Kubo, Naoki; Yoneshima, Yasuto; Inoue, Hiroyuki; Tanaka, Kentaro; Osoegawa, Atsushi; Tagawa, Tetsuzo; Nakanishi, Yoichi; Okamoto, Isamu
• Is Part Of: Cancer science. Volume 111:Issue 7(2020)
• Page Start: 2482
• Page End: 2487
• Publication Date: 2020-06-10
• Subjects: cancer‐related gene -- idiopathic pulmonary fibrosis -- lung cancer -- next‐generation sequencing -- somatic alteration; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14488
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : The genetic basis of idiopathic pulmonary fibrosis‐associated lung cancer remains largely unknown. We show that somatic alterations were frequently identified in fibrosing lung tissue as much as that in tumor tissue, and that genes related to the RAS‐RAF signaling pathway were frequently altered in both specimens. These findings can provide a basis for the development of targeted drugs for such tumors.