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

by John, Thomas , Mitchell, Paul L. , Wong, Nicholas C. , Murone, Carmel , Dobrovic, Alexander , Solomon, Benjamin , Do, Hongdo

in 45 / 45/23 / 45/77 / 631/208/176/1988 / 631/67/1612/1350 / 692/308/1892 / 692/53/2423 / BRCA1 protein / Breast cancer / Carcinoma, Non-Small-Cell Lung - genetics / Deoxyribonucleic acid / DNA / DNA methylation / DNA Methylation - genetics / DNA Repair / DNA, Neoplasm - genetics / ERCC1 protein / Genes / Genomes / Humanities and Social Sciences / Humans / Lung cancer / Lung Neoplasms - genetics / Melting / Methylation / MLH1 protein / multidisciplinary / Neoplasm Proteins - genetics / Non-small cell lung carcinoma / O6-methylguanine-DNA methyltransferase / Promoter Regions, Genetic - genetics / Science / Small cell lung carcinoma / Tumor Cells, Cultured / XPC protein

2014

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

by John, Thomas , Mitchell, Paul L. , Wong, Nicholas C. , Murone, Carmel , Dobrovic, Alexander , Solomon, Benjamin , Do, Hongdo

2014

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

by John, Thomas , Mitchell, Paul L. , Wong, Nicholas C. , Murone, Carmel , Dobrovic, Alexander , Solomon, Benjamin , Do, Hongdo

2014

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Journal Article

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

John, Thomas,

Mitchell, Paul L.,

Wong, Nicholas C.,

Murone, Carmel,

Dobrovic, Alexander,

Solomon, Benjamin,

Do, Hongdo

2014

Overview

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.

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Nature Publishing Group UK,Nature Publishing Group

Subject

/ 45/23

/ 45/77