Journal Article Ahead of print
PubMed: 41586908 DOI: 10.1007/s00428-026-04417-1
Selective MYC 5' amplification in postirradiation/lymphedema-associated angiosarcoma.
Virchows Arch
Authors: Naohiro Makise, Ryuta Kojima, Naoki Takeda, Mariko Oikawa, Yusuke Amano, Takahiro Sugiyama, Shouko Hayama, Rikiya Nakamura, Hideyuki Kinoshita, Hiroto Kamoda, Yoko Hagiwara, Tsukasa Yonemoto, Masahito Kawazu, Akinobu Araki
Affiliations
- Division of Surgical Pathology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8717, Japan.
- Division of Cell Therapy, Chiba Cancer Center, Chiba, Japan.
- Division of Surgical Pathology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8717, Japan.
- Department of Breast Surgery, Chiba Cancer Center, Chiba, Japan.
- Department of Orthopaedic Surgery, Chiba Cancer Center, Chiba, Japan.
Abstract
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.
MeSH
Genes, Myc, Cells, Breast Neoplasms, Hemangiosarcoma, Neoplasms, Pathology, Chromatin Immunoprecipitation, Chromatin, Immunoprecipitation, Breast, Enhancer Elements, Genetic, Data Analysis, Endothelium, Lymphedema