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Abnormal Proliferation02:23

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

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

Naohiro Makise1, Ryuta Kojima2, Naoki Takeda3

  • 1Division of Surgical Pathology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8717, Japan. makise58@gmail.com.

Virchows Archiv : an International Journal of Pathology
|January 26, 2026
PubMed
Summary

MYC break-apart FISH helps distinguish postirradiation/lymphedema-associated angiosarcoma (PLAS) from carcinoma. Amplification patterns suggest an endothelium-specific enhancer co-amplifies with MYC in PLAS.

Keywords:
MYCAngiosarcomaBreastFluorescence in situ hybridization

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Postirradiation/lymphedema-associated angiosarcoma (PLAS) is a rare malignancy.
  • The role of MYC gene amplification in PLAS pathogenesis is not fully understood.
  • Distinguishing PLAS from other carcinomas can be challenging.

Purpose of the Study:

  • To investigate the co-amplification of an endothelium-specific enhancer with the MYC gene in PLAS.
  • To evaluate the diagnostic utility of MYC break-apart fluorescence in situ hybridization (FISH) for differentiating PLAS from carcinoma.
  • To analyze the association between MYC-co-amplified regions and cell type-specific enhancers.

Main Methods:

  • MYC break-apart FISH was performed on six PLAS cases and 23 MYC-amplified carcinoma cases.
  • MYC-co-amplified regions were analyzed using cBioportal.
  • Endothelium-specific active enhancers were identified using ENCODE chromatin immunoprecipitation-sequencing data (H3K4me1 and H3K27ac).

Main Results:

  • Selective 5' MYC amplification was observed in all PLAS cases.
  • Carcinomas, including breast cancers, showed dual-signal MYC amplification.
  • Angiosarcoma exhibited 5' skewing of the MYC-co-amplified region, linked to an endothelium-specific enhancer upstream of MYC.

Conclusions:

  • MYC break-apart FISH is a valuable tool for distinguishing PLAS from carcinoma.
  • The findings support the hypothesis of MYC co-amplification with an endothelium-specific enhancer in PLAS.
  • Further research with larger cohorts and advanced genomic/epigenetic techniques is warranted.