|Title||CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Vasilatos SN, Broadwater G, Barry WT, Baker JC, Lem S, Dietze EC, Bean GR, Bryson AD, Pilie PG, Goldenberg V, Skaar D, Paisie C, Torres-Hernandez A, Grant TL, Wilke LG, Ibarra-Drendall C, Ostrander JH, D'Amato NC, Zalles C, Jirtle R, Weaver VM, Seewaldt VL|
|Journal||Cancer Epidemiol Biomarkers Prev|
|Date Published||2009 Mar|
|Keywords||Biopsy, Fine-Needle, Breast Neoplasms, Chi-Square Distribution, CpG Islands, Cyclin-Dependent Kinase Inhibitor p16, Cytokines, DNA Methylation, Female, Genes, BRCA1, Genes, BRCA2, Genes, Tumor Suppressor, Humans, Mutation, Polymerase Chain Reaction, Premenopause, Promoter Regions, Genetic, Receptors, Progesterone, Receptors, Retinoic Acid, Risk, Risk Assessment, Statistics, Nonparametric, Tumor Suppressor Proteins|
BACKGROUND: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known.
METHODS: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1.
RESULTS: Although the overall frequency of CpG island promoter methylation events increased with age (P<0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P=0.051), INK4a/ARF (P=0.042), HIN-1 (P=0.044), and PRA (P=0.032), as well as the overall frequency of methylation events (P=0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had
CONCLUSIONS: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.
|Alternate Journal||Cancer Epidemiol. Biomarkers Prev.|
|PubMed Central ID||PMC2667866|
|Grant List||2P30CA14236-26 / CA / NCI NIH HHS / United States |
CA68438-AV13 / CA / NCI NIH HHS / United States
R01 CA088799-01A1 / CA / NCI NIH HHS / United States
R01 CA088799-06A1 / CA / NCI NIH HHS / United States
R01 CA088799-08S1 / CA / NCI NIH HHS / United States
R01 CA098441-05 / CA / NCI NIH HHS / United States
R01 CA114068-03 / CA / NCI NIH HHS / United States
R01 CA155664 / CA / NCI NIH HHS / United States
R01CA114068 / CA / NCI NIH HHS / United States
R01CA88799 / CA / NCI NIH HHS / United States
R01CA98441 / CA / NCI NIH HHS / United States