BRCA1 promoter methylation in sporadic breast tumors: Relationship to gene expression profiles

Evan Matros, Zhigang C. Wang, Gabriela Lodeiro, Alexander Miron, J. Dirk Iglehart, Andrea L. Richardson

Research output: Contribution to journalArticlepeer-review

Abstract

BRCA1 is a tumor suppressor gene that functions in DNA repair. Basal-like tumors are a distinctive subtype of breast cancer defined by gene expression profiles. Hereditary BRCA1 breast tumors and basal-like sporadic tumors have a similar phenotype and gene expression signature, suggesting involvement of BRCA1 in the pathogenesis of sporadic basal-like cancer. This study evaluates the role of BRCA1 in sporadic breast tumorigenesis. BRCA1 protein expression and promoter methylation are compared to tumor histopathology and gene expression profiles. We find BRCA1 protein expression correlates with tumor mitotic rate, consistent with normal cell-cycle regulation of the BRCA1 gene. Methylation is found in 21% of tumors and is associated with lower BRCA1 protein, but not with specific pathologic features. Basal-like tumors, defined by hierarchical clustering of gene expression, have infrequent BRCA1 methylation and high levels of BRCA1 protein expression consistent with their high mitotic rate. Tumors with BRCA1 promoter methylation are present in all expression clusters; however, a subgroup of ER-positive high-grade tumors has a significantly greater number of BRCA1 methylated tumors. Absence of BRCA1 promoter methylation and high levels of BRCA1 expression in basal-like sporadic tumors suggest alternate explanations for the phenotypic similarities of these tumors to hereditary BRCA1 tumors.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalBreast Cancer Research and Treatment
Volume91
Issue number2
DOIs
StatePublished - May 1 2005
Externally publishedYes

Keywords

  • BRCA1
  • Basal-like breast cancer
  • Gene expression arrays
  • Methylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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