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Distinct clinical features and outcomes in never-smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement.

Authors
 Hye Ryun Kim  ;  Hyo Sup Shim  ;  Jin-Haeng Chung  ;  Young Joo Lee  ;  Yun Kyoung Hong  ;  Sun Young Rha  ;  Se Hoon Kim  ;  Sang-Jun Ha  ;  Se Kyu Kim  ;  Kyung Young Chung  ;  Ross Soo  ;  Joo Hang Kim  ;  Byoung Chul Cho 
Citation
 CANCER, Vol.118(3) : 729-739, 2012 
Journal Title
 CANCER 
ISSN
 0008-543X 
Issue Date
2012
MeSH
Adenocarcinoma/genetics ; Adenocarcinoma/mortality ; Adenocarcinoma/secondary ; Adult ; Aged ; Carcinoma, Large Cell/genetics ; Carcinoma, Large Cell/mortality ; Carcinoma, Large Cell/secondary ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/secondary ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/secondary ; Female ; Gene Rearrangement* ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation/genetics* ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Proto-Oncogene Proteins p21(ras) ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptor, Epidermal Growth Factor/genetics* ; Smoking* ; Survival Rate ; ras Proteins/genetics*
Keywords
Adenocarcinoma/genetics ; Adenocarcinoma/mortality ; Adenocarcinoma/secondary ; Adult ; Aged ; Carcinoma, Large Cell/genetics ; Carcinoma, Large Cell/mortality ; Carcinoma, Large Cell/secondary ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/secondary ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/secondary ; Female ; Gene Rearrangement* ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation/genetics* ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Proto-Oncogene Proteins p21(ras) ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptor, Epidermal Growth Factor/genetics* ; Smoking* ; Survival Rate ; ras Proteins/genetics*
Abstract
BACKGROUND: The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype-specific subsets of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS: The authors concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from 229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression-free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87; P = .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P = .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never-smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype-specific subsets can lead to successful treatment with appropriate kinase inhibitors. Copyright © 2011 American Cancer Society.
Files in This Item:
T201200216.pdf Download
DOI
21720997
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Kyu(김세규)
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Chung, Kyung Young(정경영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hong, Yun Kyoung(홍윤경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89847
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