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Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis
Author(s) -
Hata Atsushi,
Nakajima Takahiro,
Matsusaka Keisuke,
Fukuyo Masaki,
Nakayama Manabu,
Morimoto Junichi,
Ito Yuki,
Yamamoto Takayoshi,
Sakairi Yuichi,
Rahmutulla Bahityar,
Ota Satoshi,
Wada Hironobu,
Suzuki Hidemi,
Iwata Takekazu,
Matsubara Hisahiro,
Ohara Osamu,
Yoshino Ichiro,
Kaneda Atsushi
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33499
Subject(s) - idiopathic pulmonary fibrosis , cdkn2a , lung cancer , medicine , cancer research , pathology , cancer , oncology , lung
Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF‐associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF‐associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2 ; 38% vs 10%, P = .04 for NFE2L2 ). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation ( P = .02 for TP53 and P = .06 for CDKN2A ). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis ( P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.