Determining the Frequency of MAGI3-AKT3 Gene Rearrangements in Triple Negative Breast Cancer
Sonal Varma, Juan Miguel Mosquera, Theresa Y MacDonald, Mark A Rubin, Sandra J Shin. Weill Cornell Medical College, New York, NY
Background: Discovery of recurrent gene rearrangements is a relatively new avenue in breast cancer. Recently, MAGI3-AKT3 fusion has been reported to be present in 7% of triple negative-basal like subtype of breast cancer (5 out of 72 cases in Banerji et al. Nature 2012). The clinical implications are significant since the confirmation of this discovery may offer novel treatments with small molecule AKT kinase inhibitors. We assessed MAGI3-AKT3 gene rearrangements in triple negative breast cancer using fluorescence in situ hybridization (FISH).
Design: 154 triple negative breast cancer cases predominantly from a Caucasian population were studied. Three cores from each case were represented in tissue microarrays (TMAs) and interrogated using locus-specific, dual-color break-apart FISH assays for MAGI3 and AKT3 genes, and a fusion assay for MAGI3-AKT3.
Results: No MAGI3 or AKT3 break apart signals were identified by FISH in any of the 154 cases. At least 50 nuclei per core were evaluated using a fluorescence microscope.
Conclusions: The absence of MAGI3-AKT3 gene rearrangements by FISH in our patient population suggests a possibility that the recently described MAGI3-AKT3 gene fusion occurs at the transcript level only. Our study has the statistical power to detect gene rearrangements that occur at a frequency of as low as 3% with 95% confidence. Therefore we can reliably deduce that if these genetic alterations are present, they are much less frequent than that reported in the above study (7 %). Alternatively, it may be population-specific since the patient cohort where this gene fusion was identified was comprised of Mexican and Vietnamese ethnicities only. Our findings have important clinical implications: Further studies are needed to determine whether MAGI3-AKT3 gene rearrangements are recurrent events at the genomic level and enriched in triple-negative breast cancer, which may translate in benefit from ATP-competitive AKT inhibitors.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 22, Tuesday Morning