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

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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number4186
Number of pages8
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 26 Feb 2014
Externally publishedYes

Cite this

Do, Hongdo ; Wong, Nicholas C. ; Murone, Carmel ; John, Thomas ; Solomon, Benjamin ; Mitchell, Paul L. ; Dobrovic, Alexander. / A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma. In: Scientific Reports. 2014 ; Vol. 4.
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title = "A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma",
abstract = "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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A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma. / Do, Hongdo; Wong, Nicholas C.; Murone, Carmel; John, Thomas; Solomon, Benjamin; Mitchell, Paul L.; Dobrovic, Alexander.

In: Scientific Reports, Vol. 4, 4186, 26.02.2014.

Research output: Contribution to journalArticleResearchpeer-review

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