Selective MYC 5' amplification in postirradiation/lymphedema-associated angiosarcoma

We assessed whether an endothelium-specific enhancer is co-amplified with MYC in postirradiation/lymphedema-associated angiosarcoma (PLAS). First, the signal pattern and diagnostic utility of MYC break-apart fluorescence in situ hybridization (FISH) were examined to distinguish PLAS from carcinoma. Next, public data were analyzed to determine the association between the MYC-co-amplified region and cell type-specific active enhancers. Six cases of PLAS were retrieved, including three with a history of breast cancer. Additionally, we retrieved 23 MYC-amplified carcinoma cases, of which seven were breast cancers. MYC break-apart FISH was performed in all cases. The MYC-co-amplified regions in angiosarcoma and other carcinomas were explored using cBioportal. Endothelium-specific active enhancers were searched using H3K4me1 and H3K27ac chromatin immunoprecipitation-sequencing data on ENCODE. MYC break-apart FISH analysis revealed selective 5' amplification in all six PLAS cases, whereas 16 of 23 carcinomas, as well as six of seven MYC-amplified breast cancers, exhibited dual-signal amplification. cBioportal data analysis revealed 5' skewing of the MYC-co-amplified region in angiosarcoma, which was not readily apparent in other carcinomas. ENCODE chromatin immunoprecipitation-sequencing data analysis revealed endothelium-specific active enhancers upstream of MYC; the cell/tissue-type-specific 3' enhancer was not conspicuous. In conclusion, MYC break-apart FISH is a useful adjunctive tool for distinguishing PLAS from carcinoma. The 5' skewing of the MYC-co-amplified region, possibly associated with an endothelium-specific active enhancer, was confirmed. Subsequent studies involving larger case series, higher-resolution genomic experiments, and single-cell epigenetic experiments are required.