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[88] BRCA2 Deficiency and EMSY Amplification; Possible Mutually Exclusive Genetic Events in the Development of Breast Cancer

AL Bane, N Weerasooriya, IL Andrulis, FP O'Malley. Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

Background: BRCA1 and BRCA2 are two highly penetrant breast cancer susceptibility genes implicated in 30-50% of familial breast cancers. Both genes are considered classic tumor suppressors with inactivation or loss of both alleles required for tumorigenesis. In addition, approximately 10% of sporadic breast cancers have lost functional BRCA1 through a combination of LOH and/or epigenetic silencing. More recently a potential mechanism for BRCA2 inactivation in sporadic breast and ovarian cancers has been described; EMSY a gene located on 11q13.5, interacts with exon 3 of BRCA2 and has been shown in vitro to transcriptionally silence it. This implies that EMSY amplification is functionally equivalent to a BRCA2 null phenotype. EMSY amplification has been shown to occur in 9-13% of sporadic breast cancers; however the presence or absence of EMSY amplification has not been studied in BRCA2-associated cancers. The objective of our study was to determine the frequency of EMSY amplification in BRCA2-associated and control tumors.
Design: TMAs were constructed using 64 BRCA2-associated tumors and 186 age and ethnically matched control tumors accrued through the Ontario Familial Breast Cancer Registry. TMA sections were analyzed for EMSY gene status using FISH. TMA sections were additionally analysed for the expression of hormone receptors, HER2/neu protein, basal and luminal cytokeratins.
Results: None (0%) of BRCA2-associated tumors were found to have EMSY amplification as compared to 11 (9%) of the control tumors, (p=0.03). Those tumors with EMSY amplification when compared with non-amplified tumors showed no statistically significant differences with regards to tumor grade, hormonal status or expression of HER2/neu, basal or luminal cytokeratins.
Conclusions: We have shown that BRCA2-associated tumors do not exhibit EMSY amplification, whereas this gene is amplified in approximately 9% of sporadic breast tumors. Those tumors with EMSY amplification do not have a distinguishing phenotype as determined by immunohistochemical profiling. These results suggest that BRCA2 deficiency and EMSY amplification may be mutually exclusive genetic events on the road to tumorigenesis.
Category: Breast

Monday, March 26, 2007 8:00 AM

Platform Session: Section D, Monday Morning