title: CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer.
abstract: DNA methylation occurs commonly in non-small cell lung cancer (NSCLC). We sought to determine the frequency and relationship of methylation of key genes involved in the pathways of mitotic checkpoint control, DNA damage repair, apoptosis, and growth factor signaling in these patients. We analyzed the DNA methylation status of eight genes (CHFR, FANCF, MGMT, p16, DAPK, ASC or TMS-1, RAR-B, and CRBP1) using nested methylation-specific PCR (MSP) on over 314 paraffin-embedded, human non-small cell lung cancer samples. We determined the methylation frequency of each gene in addition to the association of the methylation of each gene with other members of the panel. Methylation was a common event in these samples. Our methylation analysis showed frequencies of methylation of 10% for CHFR, 14% for FANCF, 30% for MGMT, 29% for p16, 17% for DAPK, 33% for ASC, 38% for RAR-B, and 7% for CRBP1. There was a strong correlation between methylation of the mitotic G2-M checkpoint gene, CHFR, and methylation of other genes in our panel involved in DNA damage repair (FANCF and MGMT) and apoptosis (DAPK and ASC) but not with other genes in our panel, including p16 (the G1-S checkpoint gene), CRBP1, or RAR-B. In addition, MGMT methylation strongly correlated with the pro-apoptotic gene, ASC. There are distinct associations of methylated genes in non-small cell lung cancer involving DNA damage repair, apoptosis, and the G2-M mitotic checkpoint control. Further studies are warranted to determine whether these methylation patterns have implications for prognosis in addition to prediction of response to chemotherapeutic agents commonly used in the treatment of non-small cell lung cancer, such as radiotherapy and platinum- or taxane-based chemotherapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA and Oregon Clinical and Translational Research Institute, Portland, OR 97239, USA.
authors.forename: Joshi
authors.initials: J
authors.lastname: Alumkal
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Drachova
authors.affiliation: College of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Medical Genome Facility Gene Expression Core, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Serban S
authors.initials: SS
authors.lastname: Marina
authors.affiliation: Medical Genome Facility Gene Expression Core, Mayo Clinic, Rochester, MN 55905, USA and Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
mesh_terms: D000368:Aged; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases