CpG island promoter hypermethylation of the BRCA1-binding protein SRBC occurs in the context of a wild-type BRCA1 in breast cancer

1609 Imbalance of the BRCA1 pathway is a major hallmark of human breast cancer. In this context, germline point mutation and CpG island promoter hypermethylation of BRCA1 are a feature of breast neoplasms. Inactivation by promoter hypermethylation of the BRCA1-binding protein SRBC could constitute another way by which this cellular network may be altered in human cancers. If both BRCA1 and SRBC act in the same pathway, simultaneous molecular lesions in the two genes in the same tumor should be a rare event. To test whether this inverse association exists, we have analyzed the BRCA1 and BRCA2 mutational and CpG island hypermethylation status versus SRBC CpG island hypermethylation of a large collection of sporadic and inherited breast tumors. No association was found between the methylation status of SRBC and the BRCA2 mutational status. However, our results demonstrate that the epigenetic alteration of SRBC is confined to breast tumors without BRCA1 hypermethylation or BRCA1 germline mutations. Thus, the mutual exclusivity of the epigenetic and genetic alterations in BRCA1 and SRBC suggests that both genes play a critical and cooperative role in human tumorigenesis.