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


Journal Article

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

Full Text

Cited 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

Published Date

  • March 3, 2009

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 901 - 914

PubMed ID

  • 19258476

Pubmed Central ID

  • 19258476

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

International Standard Serial Number (ISSN)

  • 1055-9965

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-08-0875


  • eng