Journal Article

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

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

2020

Overview

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. 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.

• Publisher: Wiley,John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Aged / Biomarkers / cancer‐related gene / Deoxyribonucleic acid / DNA / Epidermal growth factor receptors / ErbB-3 protein / Female / Fibrosis / Genes / Genetic analysis / Genetic Association Studies / Genetic Predisposition to Disease / Genetic Testing / Genetic Variation / Genomes / Genomics / High-Throughput Nucleotide Sequencing / Histology / Humans / Idiopathic Pulmonary Fibrosis / Lung cancer / Lung diseases / Lung Neoplasms / Male / Middle Aged / Mutation / Neoplasm Staging / next‐generation sequencing / Non-small cell lung carcinoma / Original / Original Articles / p53 Protein / Patients / Pulmonary fibrosis / Raf protein / Ribonucleic acid / RNA / Sequence Analysis, DNA / Signal transduction / somatic alteration / Tumorigenesis