Paired genetic analysis by next-generation sequencing of lung cancer and associated idiopathic pulmonary fibrosis.
Adult
Aged
Biomarkers
Female
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Genetic Testing
Genetic Variation
High-Throughput Nucleotide Sequencing
Humans
Idiopathic Pulmonary Fibrosis
/ diagnosis
Lung Neoplasms
/ diagnosis
Male
Middle Aged
Neoplasm Staging
Sequence Analysis, DNA
cancer-related gene
idiopathic pulmonary fibrosis
lung cancer
next-generation sequencing
somatic alteration
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
11
03
2020
revised:
11
05
2020
accepted:
13
05
2020
pubmed:
20
5
2020
medline:
11
8
2020
entrez:
20
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32426915
doi: 10.1111/cas.14488
pmc: PMC7385390
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2482-2487Informations de copyright
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Cancer Res. 1992 Nov 1;52(21):6079-82
pubmed: 1394234
Blood. 2013 Oct 3;122(14):2443-52
pubmed: 23982172
Cancer Sci. 2020 Jul;111(7):2482-2487
pubmed: 32426915
J Thorac Oncol. 2011 May;6(5):942-6
pubmed: 21623265
N Engl J Med. 2014 Dec 4;371(23):2167-77
pubmed: 25470694
Gastroenterol Res Pract. 2016;2016:9408190
pubmed: 27781065
Lancet Respir Med. 2018 Feb;6(2):86-88
pubmed: 29241977
Oncogene. 2015 Oct;34(43):5447-59
pubmed: 25684140
Nat Rev Mol Cell Biol. 2016 Nov;17(11):722-735
pubmed: 27507209
N Engl J Med. 2009 Sep 3;361(10):947-57
pubmed: 19692680
Hum Pathol. 2001 Oct;32(10):1043-9
pubmed: 11679937
Cell. 1997 Feb 7;88(3):323-31
pubmed: 9039259
Cancer. 1973 May;31(5):1078-86
pubmed: 4705148
N Engl J Med. 2014 Nov 20;371(21):1963-71
pubmed: 25264305
Respir Res. 2017 Jun 15;18(1):120
pubmed: 28619094
Nat Rev Mol Cell Biol. 2008 May;9(5):402-12
pubmed: 18431400
Am J Med. 1968 Aug;45(2):211-9
pubmed: 5666649
J Pathol. 2018 Jan;244(1):25-35
pubmed: 28862766
Thorax. 1980 Jul;35(7):496-9
pubmed: 7434310
Cell. 2004 Mar 19;116(6):855-67
pubmed: 15035987
JCO Precis Oncol. 2018 Nov;2:1-24
pubmed: 35135139
Am J Respir Crit Care Med. 2008 Jun 15;177(12):1348-57
pubmed: 18337594
Cancer. 2002 Aug 1;95(3):624-33
pubmed: 12209756
Tohoku J Exp Med. 1992 Jul;167(3):231-7
pubmed: 1488744
Mol Cell Biol. 1994 Jun;14(6):3550-8
pubmed: 7515147
N Engl J Med. 2013 Jun 20;368(25):2385-94
pubmed: 23724913
Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68
pubmed: 30168753
Science. 2008 Sep 12;321(5895):1499-502
pubmed: 18787170
Lancet Oncol. 2016 Jul;17(7):984-993
pubmed: 27283860
N Engl J Med. 2004 May 20;350(21):2129-39
pubmed: 15118073
Cancer Discov. 2015 Aug;5(8):842-9
pubmed: 25971939
Chest. 2015 Jan;147(1):157-164
pubmed: 25166895
Acta Pathol Jpn. 1987 Jan;37(1):11-9
pubmed: 3033984
Lancet Respir Med. 2017 Jan;5(1):42-50
pubmed: 27825616
Nature. 2017 Aug 10;548(7666):234-238
pubmed: 28783719
J Carcinog. 2004 Mar 26;3:6
pubmed: 15046639
Nat Rev Cancer. 2008 Apr;8(4):253-67
pubmed: 18354415