CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis Export

@article{citeulike:4163451, abstract = {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 [\&le;]4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):901-14) 10.1158/1055-9965.EPI-08-0875}, author = {Vasilatos, Shauna N. and Broadwater, Gloria and Barry, William T. and Baker, Joseph C. and Lem, Siya and Dietze, Eric C. and Bean, Gregory R. and Bryson, Andrew D. and Pilie, Patrick G. and Goldenberg, Vanessa and Skaar, David and Paisie, Carolyn and Torres-Hernandez, Alejandro and Grant, Tracey L. and Wilke, Lee G. and Ibarra-Drendall, Catherine and Ostrander, Julie H. and D'Amato, Nicholas C. and Zalles, Carola and Jirtle, Randy and Weaver, Valerie M. and Seewaldt, Victoria L.}, citeulike-article-id = {4163451}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1055-9965.EPI-08-0875}, citeulike-linkout-1 = {http://cebp.aacrjournals.org/cgi/content/abstract/18/3/901?etoc}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19258476}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19258476}, day = {1}, doi = {10.1158/1055-9965.EPI-08-0875}, journal = {Cancer Epidemiol Biomarkers Prev}, keywords = {brca, breast, cimp, gene\_specific\_methylation, methylation}, month = {March}, number = {3}, pages = {901--914}, posted-at = {2009-03-11 01:12:04}, priority = {2}, title = {CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis}, url = {http://dx.doi.org/10.1158/1055-9965.EPI-08-0875}, volume = {18}, year = {2009} }

TY - JOUR ID - citeulike:4163451 L3 - citeulike-article-id:4163451 N2 - 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 [&le;]4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):901-14) 10.1158/1055-9965.EPI-08-0875 IS - 3 JF - Cancer Epidemiol Biomarkers Prev EP - 914 TI - CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis VL - 18 SP - 901 KW - brca KW - breast KW - cimp KW - gene_specific_methylation KW - methylation AU - Vasilatos, Shauna AU - Broadwater, Gloria AU - Barry, William AU - Baker, Joseph AU - Lem, Siya AU - Dietze, Eric AU - Bean, Gregory AU - Bryson, Andrew AU - Pilie, Patrick AU - Goldenberg, Vanessa AU - Skaar, David AU - Paisie, Carolyn AU - Torres-Hernandez, Alejandro AU - Grant, Tracey AU - Wilke, Lee AU - Ibarra-Drendall, Catherine AU - Ostrander, Julie AU - D'Amato, Nicholas AU - Zalles, Carola AU - Jirtle, Randy AU - Weaver, Valerie AU - Seewaldt, Victoria PY - 2009/03/01/ UR - http://dx.doi.org/10.1158/1055-9965.EPI-08-0875 ER -