| Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis. | |
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MedLine Citation:
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PMID: 22317764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Our previous study revealed that 90% [47 of 52; 95% confidence interval (CI), 0.79-0.96] of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma. EXPERIMENTAL DESIGN: Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histologic subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutational status of these genes. RESULTS: Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (P < 0.001), whereas patients harboring HER2 mutations were significantly younger (P = 0.036). Higher prevalence of KRAS (P = 0.028) and HER2 (P = 0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (P = 0.002). Multivariate analysis revealed that older age at diagnosis (P = 0.013) and acinar predominant subtype (P = 0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (P = 0.030) and IMA (P = 0.017). IMA (P = 0.006) and poor differentiation (P = 0.028) were independently associated with KRAS mutations. CONCLUSIONS: The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histologic subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies. |
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Authors:
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Yang Zhang; Yihua Sun; Yunjian Pan; Chenguang Li; Lei Shen; Yuan Li; Xiaoyang Luo; Ting Ye; Rui Wang; Haichuan Hu; Hang Li; Lei Wang; William Pao; Haiquan Chen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-02-08 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 18 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-04-04 Completed Date: 2012-08-23 Revised Date: 2013-04-03 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 1947-53 Citation Subset: IM |
Copyright Information:
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©2012 AACR. |
Affiliation:
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Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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genetics*,
pathology Adult Age Factors Aged Aged, 80 and over DNA Mutational Analysis Female Gene Frequency Genotype Humans Logistic Models Lung Neoplasms / genetics*, pathology Middle Aged Multivariate Analysis Mutation* Neoplasm Staging Oncogenes / genetics* Proto-Oncogene Proteins B-raf / genetics Receptor Protein-Tyrosine Kinases / genetics Receptor, Epidermal Growth Factor / genetics Receptor, erbB-2 / genetics Smoking Young Adult ras Proteins / genetics |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA121210-01A1/CA/NCI NIH HHS; R01 CA121210-02/CA/NCI NIH HHS; R01 CA121210-03/CA/NCI NIH HHS; R01 CA121210-04/CA/NCI NIH HHS; R01 CA121210-05/CA/NCI NIH HHS; R01-CA121210/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.10.1/anaplastic lymphoma kinase; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 3.6.5.2/ras Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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