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CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.


ABSTRACT: 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.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.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

SUBMITTER: Vasilatos SN 

PROVIDER: S-EPMC2667866 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.

Vasilatos Shauna N SN   Broadwater Gloria G   Barry William T WT   Baker Joseph C JC   Lem Siya S   Dietze Eric C EC   Bean Gregory R GR   Bryson Andrew D AD   Pilie Patrick G PG   Goldenberg Vanessa V   Skaar David D   Paisie Carolyn C   Torres-Hernandez Alejandro A   Grant Tracey L TL   Wilke Lee G LG   Ibarra-Drendall Catherine C   Ostrander Julie H JH   D'Amato Nicholas C NC   Zalles Carola C   Jirtle Randy R   Weaver Valerie M VM   Seewaldt Victoria L VL  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20090303 3


<h4>Background</h4>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.<h4>Methods</h4>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, P  ...[more]

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