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Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment 期刊论文

编号：

8c21bd81-7906-4c95-a4c3-25629836f5e7
作者：

Niu, Xiaomin^[1] Liu, Fatao^[2,3] Zhou, Yi^[4] Zhou, Zhen^[1] Zhou, Daizhan^[5] Wang, Ting^[2,3] Li, Ziming^[1] Ye, Xiangyun^[1] Yu, Yongfeng^[1] Weng, Xiaoling^[6,7] Zhang, Hong^[6,7] Ye, Junyi^[6,7] Liao, Meilin^[1] Liu, Yun^[6] Chen, Zhiwei^[1] Lu, Shun^[1]
语种：

English
期刊：

CLINICAL CANCER RESEARCH ISSN：1078-0432 2017 年 23 卷 17 期 (5003 - 5014) ; SEP 1
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摘要：

Purpose: The past decade has witnessed the rapid development of personalized targeted therapies in lung cancer. It is still unclear whetherepigeneticchangesare involved in the responseto tyrosine kinase inhibitor (TKI) treatment in epidermal growth factor receptor (EGFR)-mutated lung cancer. Experimental Design: Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the methylation changes in paired tissues before and after erlotinib treatment for 42 days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients (N = 2) with EGFR 19 deletion. The Sequenom EpiTYPER assay was used to validate the changed methylated candidate genes. Up-or downregulation of the candidate gene was performed to elucidate the potential mechanism in the regulation of erlotinib treatment response. Results: Sixty aberrant methylated genes were screened using MSCC sequencing. Two aberrant methylated genes, CBFA2T3 and GABBR2, were clearly validated. A same differential methylated region (DMR) between exon 2 and exon 3 of GABBR2 gene was confirmed consistently in both patients. GABBR2 was significantly downregulated in EGFR 19 deletion cells, HCC4006 and HCC827, but remained conserved in EGFR wild-type A549 cells after erlotinib treatment. Upregulation of GABBR2 expression significantly rescued erlotinib-induced apoptosis in HCC827 cells. GABBR2 was significantly downregulated, along with the reduction of S6, p-p70 S6, and p-ERK1/2, demonstrating that GABBR2 may play an important role in EGFR signaling through the ERK1/2 pathway. Conclusions: We demonstrated that GABBR2 gene might be a novel potential epigenetic treatment target with induction erlotinib treatment for stage IIIa (N2) EGFR 19 deletion lung adenocarcinoma. (C) 2017 AACR.
推荐引用方式
GB/T 7714：

Niu Xiaomin,Liu Fatao,Zhou Yi, et al. Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment [J].CLINICAL CANCER RESEARCH,2017,23(17):5003-5014.
APA：

Niu Xiaomin,Liu Fatao,Zhou Yi,Zhou Zhen,&Lu Shun.(2017).Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment .CLINICAL CANCER RESEARCH,23(17):5003-5014.
MLA：

Niu Xiaomin, et al. "Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment" .CLINICAL CANCER RESEARCH 23,17(2017):5003-5014.

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