A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma

被引：37

作者：

Do, Hongdo ^{[1
,2
,6
]}

Wong, Nicholas C. ^{[2
,6
]}

Murone, Carmel ^{[2
]}

John, Thomas ^{[3
]}

Solomon, Benjamin ^{[4
,5
]}

Mitchell, Paul L. ^{[3
]}

Dobrovic, Alexander ^{[1
,2
,4
,5
,6
]}

机构：

[1] Peter MacCallum Canc Ctr, Dept Pathol, Mol Pathol Res & Dev Lab, Melbourne, Vic 8006, Australia

[2] Austin Hosp, Olivia Newton John Canc & Wellness Ctr, Ludwig Inst Med Res, Translat Genom & Epigen Lab, Heidelberg, Vic 3084, Australia

[3] Austin Hosp, Olivia Newton John Canc & Wellness Ctr, Joint Austin Ludwig Med Oncol Dept, Heidelberg, Vic 3084, Australia

[4] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia

[5] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic 8006, Australia

[6] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

英国医学研究理事会;

关键词：

MESSENGER-RNA EXPRESSION; CISPLATIN-BASED CHEMOTHERAPY; CLINICAL-RESPONSE; BRCA1; PROMOTER; P53; MUTATION; CANCER; HYPERMETHYLATION; INACTIVATION; ERCC1; TUMOR;

D O I：

10.1038/srep04186

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DNA repair genes that have been inactivated by promoter methylation offer potential therapeutic targets either by targeting the specific repair deficiency, or by synthetic lethal approaches. This study evaluated promoter methylation status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1, RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell lines using the methylation-sensitive high resolution melting (MS-HRM) methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT methylation was detected in 13% of the NSCLCs. Contrary to previous studies, methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer Genome Atlas (TCGA) was consistent with these findings. The study emphasises the importance of using appropriate methodology for accurate assessment of promoter methylation.

引用

页数：8

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