Identification of an MLL4-GPS2 fusion as an oncogenic driver of undifferentiated spindle cell sarcoma in a child

Genes Chromosomes Cancer. 2014 Dec;53(12):991-8. doi: 10.1002/gcc.22208. Epub 2014 Aug 19.

Abstract

Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood entity, essentially a waste-basket for cases failing to fulfill criteria for better-established diagnoses based on combined histology, immunohistochemistry, and tumor genetic assays. We identified a novel chromosomal translocation t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in an in-frame fusion gene MLL4-GPS2, the expression of which promotes anchorage-independent growth. MLL4 was previously reported to be similarly rearranged in hepatocellular carcinomas, notably those positive for hepatitis B virus. Isolated reports of individual rearrangements of GPS2 in a prostate carcinoma cell line and in glioblastoma multiforme, each with different partner genes, recently emerged from high-throughput sequencing studies but have not been further evaluated for biological effect.

Keywords: Health Research Board of Ireland (CSA/2012/13); National Children's Research Centre.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Child
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Cohort Studies
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Fusion*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Middle Aged
  • NIH 3T3 Cells
  • Oncogene Proteins, Fusion / metabolism*
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Sarcoma / therapy
  • Translocation, Genetic
  • Young Adult

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • MLL4-GPS2 fusion protein, human
  • Oncogene Proteins, Fusion