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EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma.

ABSTRACT: In this study, EGFR-activating mutation status and DNA copy number abundances of members of ErbB family were measured in 261 lung adenocarcinomas. The associations between DNA copy number abundances of ErbB family, EGFR-activating mutation status, and prognosis were explored. Results showed that DNA copy number abundances of EGFR, ERBB2, ERBB3, and ERBB4 had associations with overall survival in lung adenocarcinoma with EGFR-activating mutations. In the stratification analysis, only ERBB2 showed significant discrepancy in patients carrying wild type EGFR and other members of ErbB family in patients carrying EGFR-activating mutation. This indicated that CNAs of ErbB family had effect modifications of EGFR-activating mutation status. Findings of this study demonstrate potential molecular guidance of patient management of lung adenocarcinoma with or without EGFR-activating mutations.

SUBMITTER: Chen HY

PROVIDER: S-EPMC4891022 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma.

Chen Hsuan-Yu HY Liu Chia-Hsin CH Chang Ya-Hsuan YH Yu Sung-Liang SL Ho Bing-Ching BC Hsu Chung-Ping CP Yang Tsung-Ying TY Chen Kun-Chieh KC Hsu Kuo-Hsuan KH Tseng Jeng-Sen JS Hsia Jiun-Yi JY Chuang Cheng-Yen CY Chang Chi-Sheng CS Li Yu-Cheng YC Li Ker-Chau KC Chang Gee-Chen GC Yang Pan-Chyr PC

Oncotarget 20160201 8

In this study, EGFR-activating mutation status and DNA copy number abundances of members of ErbB family were measured in 261 lung adenocarcinomas. The associations between DNA copy number abundances of ErbB family, EGFR-activating mutation status, and prognosis were explored. Results showed that DNA copy number abundances of EGFR, ERBB2, ERBB3, and ERBB4 had associations with overall survival in lung adenocarcinoma with EGFR-activating mutations. In the stratification analysis, only ERBB2 showed ...[more]

PMID: 26824984

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Project description:Background: Lung adenocarcinoma (LUAD) possesses a poor prognosis with a low 5-year survival rate even for stages I-III resected patients, it is thus critical to understand the determinants that affect the survival and discover new potentially prognostic biomarkers. Somatic copy number alterations (CNAs) are major source of genomic variations driving tumor evolution, CNAs screening may identify prognostic biomarkers. Methods: Oncoscan MIP array was used to analyze the patterns of CNAs on formalin fixed paraffin embedded(FFPE) tumor specimens from 163 consecutive stage I-III resected LUAD patients, 145 out of which received platinum-based adjuvant chemotherapy. Results: Of the 163 patients, 91(55.8%) were recurred within 3 years after surgery. The most common aberrations in our cohort were 1q, 5p, 5q, 7p, 8q, 14p, 16p, 17q, 20q for copy number gains and 8p, 9p, 13p, 16q, 18q for losses. The GISTIC2 analysis produced 45 amplification peaks and 40 deletion peaks, involving some reported genes TERT, EGFR, MYC, CCND1, CDK4, MDM2, ERBB2, NKX2-1, CCNE1, and CDKN2A, most of which were consistent with TCGA database. The amplifications of 12p12.1 (CMAS, GOLT1B, YS2, LDHB, RECQL, ETNK1, IAPP, PYROXD1, KRAS) and KDM5A were correlated with worse prognosis in our cohort, this result was further validated in 506 LUAD patients from TCGA. In addition, 163 patients could be well-classified into five groups, and the clinical outcomes were significantly different based on threshold copy number at reoccurring alteration peaks. Among the 145 patients who received adjuvant chemotherapy, focal amplification of ERBB2 and deletion of 4q34.3 were found to be specific in relapsed patients, this result was validated in an independent group of Imielinski et al., demonstrating these two CNAs may contribute to resected LUAD recurrence after adjuvant chemotherapy. Conclusion: This study suggests that CNAs profiling may be a potential prognostic classifier in resected LAUD patients. Amplifications of 12p12.1 and KDM5A might be prognostic biomarkers for LUAD, and amplification of ERBB2 and deletion of 4q34.3 predicted early relapse after adjuvant chemotherapy. These novel findings may provide implication for better implementation of precision therapy for lung cancer patients.

Dataset Information

EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma.

Publications

EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma.

Similar Datasets

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