Clinical, pathological, and genomic features of EWSR1-PATZ1 fusion sarcoma

Mod Pathol. 2019 Nov;32(11):1593-1604. doi: 10.1038/s41379-019-0301-1. Epub 2019 Jun 12.

Abstract

Molecular diagnostics of sarcoma subtypes commonly involve the identification of characteristic oncogenic fusions. EWSR1-PATZ1 is a rare fusion partnering in sarcoma, with few cases reported in the literature. In the current study, a series of 11 cases of EWSR1-PATZ1 fusion positive malignancies are described. EWSR1-PATZ1-related sarcomas occur across a wide age range and have a strong predilection for chest wall primary site. Secondary driver mutations in cell-cycle genes, and in particular CDKN2A (71%), are common in EWSR1-PATZ1 sarcomas in this series. In a subset of cases, an extended clinical and histopathological review was performed, as was confirmation and characterization of the fusion breakpoint revealing a novel intronic pseudoexon sequence insertion. Unified by a shared gene fusion, EWSR1-PATZ1 sarcomas otherwise appear to exhibit divergent morphology, a polyphenotypic immunoprofile, and variable clinical behavior posing challenges for precise classification.

MeSH terms

  • Adolescent
  • Adult
  • Aged, 80 and over
  • Brain Neoplasms / classification
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Child
  • Female
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • RNA-Binding Protein EWS / genetics*
  • Repressor Proteins / genetics*
  • Sarcoma / classification
  • Sarcoma / genetics*
  • Sarcoma / pathology*
  • Soft Tissue Neoplasms / classification
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / pathology
  • Young Adult

Substances

  • EWSR1 protein, human
  • Kruppel-Like Transcription Factors
  • Oncogene Proteins, Fusion
  • PATZ1 protein, human
  • RNA-Binding Protein EWS
  • Repressor Proteins