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Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers

Authors
 Jin Woo Ahn  ;  Han Sang Kim  ;  Jung-Ki Yoon  ;  Hoon Jang  ;  Soo Min Han  ;  Sungho Eun  ;  Hyo Sup Shim  ;  Hyun-Jung Kim  ;  Dae Joon Kim  ;  Jin Gu Lee  ;  Chang Young Lee  ;  Mi Kyung Bae  ;  Kyung Young Chung  ;  Ji Ye Jung  ;  Eun Young Kim  ;  Se Kyu Kim  ;  Joon Chang  ;  Hye Ryun Kim  ;  Joo Hang Kim  ;  Min Goo Lee  ;  Byoung Chul Cho  ;  Ji Hyun Lee  ;  Duhee Bang 
Citation
 Genome Medicine, Vol.6(18) : 1-10, 2014 
Journal Title
 Genome Medicine 
ISSN
 1756-994X 
Issue Date
2014
Abstract
BACKGROUND:Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, a comprehensive somatic mutation analysis of EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers has not been conducted. METHODS:We analyzed whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas and additional 54 tumors in two expansion cohort sets. Candidate loci were validated by target capture and Sanger sequencing. Gene set analysis was performed using Ingenuity Pathway Analysis. RESULTS:We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. These included targetable genes involved in PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase signaling (ERBB4) and genes not previously highlighted in lung adenocarcinomas, such as SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response). In the expansion cohort (N = 70), TP53 was the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, the majority of altered genes were involved in cell cycle/DNA repair (P <0.001) and cAMP-dependent protein kinase signaling (P <0.001). CONCLUSIONS:The genomic makeup of EGFR/KRAS/ALK-negative lung adenocarcinomas in never-smokers is remarkably diverse. Genes involved in cell cycle regulation/DNA repair are implicated in tumorigenesis and represent potential therapeutic targets.
Files in This Item:
T201402357.pdf Download
DOI
10.1186/gm535
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dae Joon(김대준)
Kim, Se Kyu(김세규)
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Kim, Joo Hang(김주항)
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Bae, Mi Kyung(배미경)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Ji Hyun(이지현)
Lee, Jin Gu(이진구)
Lee, Chang Young(이창영)
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
Chung, Kyung Young(정경영)
Jung, Ji Ye(정지예) ORCID logo https://orcid.org/0000-0003-1589-4142
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99288
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