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.
authors.affiliation: 1] Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, 8006, Australia [2] Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia [3] Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Hongdo
authors.initials: H
authors.lastname: Do
authors.affiliation: 1] Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia [2] Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Wong
authors.affiliation: Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia.
authors.forename: Carmel
authors.initials: C
authors.lastname: Murone
authors.affiliation: Joint Austin-Ludwig Medical Oncology Department, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: John
authors.affiliation: 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3010, Australia [2] Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, 8006, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
authors.affiliation: Joint Austin-Ludwig Medical Oncology Department, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Mitchell
authors.affiliation: 1] Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, 8006, Australia [2] Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia [3] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3010, Australia [4] Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, 8006, Australia [5] Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins