Angiosarcomas are highly malignant tumors that develop as primary angiosarcomas of unknown cause or as secondary angiosarcomas, most often following radiation therapy for breast cancer. These subsets are morphologically indistinguishable, which motivates our aim to identify genetic classifiers for diagnostic and therapeutic application. We applied the 18k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay for expression profiling of 26 primary and 29 secondary angiosarcomas. Primary and secondary angiosarcomas differed by 103 significantly de-regulated genes with up-regulation of RET, KIT, FLT4, MYC and RASGRP3 and down-regulation of CDKN2C in secondary angiosarcoma. Functional annotation analysis demonstrated involvement of multiple target genes in the receptor protein tyrosine kinase pathway. Up-regulation of RET and down-regulation of CDKN2C characterize secondary angiosarcoma, which implies a mechanistic basis for the evaluation of RET-kinase inhibitors in the treatment of these highly aggressive tumors.
Overall design
Total RNA obtained from primary and secondary angiosarcoma samples from formalin-fixed parafin-embedded samples were compared using WG-DASL. Biological replicates (two samples from the same patient, different parts of the tumor or different operation specimens) Technical replicates (two samples from the same patient and same tumor sample, analyzed in different areas of the bead chip)
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