Fusion of the genes BRD8 and PHF1 in endometrial stromal sarcoma

Genes Chromosomes Cancer. 2017 Dec;56(12):841-845. doi: 10.1002/gcc.22485. Epub 2017 Sep 6.

Abstract

We present a new endometrial stromal sarcoma (ESS)-associated genomic rearrangement involving chromosome arms 5p and 6p and leading to the formation of a BRD8-PHF1 fusion gene. The PHF1 (PHD finger protein 1) gene, from 6p21, is known to be rearranged in ESS in a promiscuous way inasmuch as it has been shown to recombine with JAZF1, EPC1, MEAF6, and now also with BRD8, in tumors of this type. In all rearrangements of PHF1, including the present one, a recurrent theme is that the entire coding part of PHF1 constitutes the 3' end of the fusion. BRD8 (bromodomain containing 8) encodes a protein which is involved in regulation of protein acetylation and/or histone acetyl transferase activity. All the genetic fusions identified so far in ESS appear to recombine genes involved in transcriptional regulation, that is, polycomb group complex-mediated and aberrant methylation/acetylation genes. This adds to the likelihood that the new BRD8-PHF1 shares the same pathogenetic mechanism as the other ESS-specific rearrangements.

MeSH terms

  • Cells, Cultured
  • Chromosomes, Human, Pair 5 / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Oncogene Fusion
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Polycomb-Group Proteins / genetics*
  • Polycomb-Group Proteins / metabolism
  • Receptors, Thyroid Hormone / genetics*
  • Receptors, Thyroid Hormone / metabolism
  • Sarcoma, Endometrial Stromal / genetics*
  • Sarcoma, Endometrial Stromal / pathology
  • Transcription Factors

Substances

  • BRD8 protein, human
  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • PHF1 protein, human
  • Polycomb-Group Proteins
  • Receptors, Thyroid Hormone
  • Transcription Factors