Abstract P6-08-03: MYC Amplification and Overexpression Discriminate Secondary from Primary Angiosarcoma of the Breast

Abstract Background: Secondary angiosarcoma of the breast is defined as a sarcoma developed in the irradiated field in patients previously treated for breast carcinoma. These tumors represent 25% to 50% of sarcomas developed after irradiation for breast cancer and are of poor outcome. Up to now, there are no criteria to distinguish primary from secondary angiosarcomas. The aim of this work was to identify molecular features able to discriminate these two types of tumors. Material and Methods: Our study was mainly based on the use of whole genome (SNP array) and whole transcriptome (mRNA and miRNA microarray) approaches. Others methods included quantitative PCR, reverse transcription quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. All patients’ records were reviewed and the clinical information about the primary and secondary sarcomas was recorded. For all radiation-induced sarcomas, the patients’ radiotherapy plans were reviewed and it was confirmed that the tumors respected the classic Cahan's criteria to confirm their secondary nature. Results: Amplification (5 to 50 fold) of the MYC oncogene was found in all breast secondary angiosarcomas (19 cases) but in none of primary angiosarcomas (6 cases) (p-value = 2.353e-05). MYC amplification was associated with mRNA and protein overexpression of this gene. In tumors with a MYC amplification, numerous genes corresponding to MYC targets and coding for mRNA or miRNAs were found to be deregulated as compared with expression levels observed in tumors without amplifications. These data point to the pathways preferentially involved in the pathogenesis of secondary angiosarcomas of the breast. The relationships between clinical, pathological and biological features are studied. Conclusions: MYC is amplified and overexpressed in secondary angiosarcomas of the breast. We suggest to exploit these characteristic features as a diagnostic criteria to distinguish primary from secondary angiosarcomas of the breast. Furthermore, those newly identified characteristics of secondary angiosarcomas could serve as a basis for tailored therapeutic approaches. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-03.