POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2

Matthew C. Hiemenz, Jaspreet Kaur, Zheng Kuang, Richard S.P. Huang, Lukas Harries, Dana Metzger, Kelsie Schiavone, Sherri Z. Millis, Douglas I. Lin, Mirna Lechpammer, Brennan Decker, Douglas A. Mata, Abhinav Reddy, Matthew Parke, Eun Y. Lee, Xiaoyan Cui, O. Hans Iwenofu, Darya Buehler, Les Henderson, Erin M. BaldwinSosipatros A. Boikos, Shakti H. Ramkissoon, Steven C. Smith

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Gene fusions involving EWSR1 or FUS as the 5′ partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3′ portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

Original languageEnglish
Pages (from-to)460-470
Number of pages11
JournalGenes Chromosomes and Cancer
Volume62
Issue number8
DOIs
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 Wiley Periodicals LLC.

Keywords

  • COLCA2
  • EWSR1
  • POU2AF3
  • comprehensive genomic profiling
  • round-cell sarcoma
  • synovial sarcoma

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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