Double minute chromosomes harboring MDM2 amplification in a pediatric atypical lipomatous tumor

Genes Chromosomes Cancer. 2019 Sep;58(9):673-679. doi: 10.1002/gcc.22754. Epub 2019 Apr 13.

Abstract

Adipocytic tumors are rare in children and are mostly benign. Less than 25 cases of pediatric well-differentiated liposarcoma (WDLPS), atypical lipomatous tumors (ALT), and dedifferentiated liposarcoma (DDLPS) have been reported. Among them, only three cases were genetically analyzed. We describe the genetic features of a rapidly growing adipose tumor that occurred in the thigh of a 7-year-old girl. Histologically, it was composed of mature adipocytic cells with a few atypia. Molecular analysis showed high-level amplification of the 12q13-21 region including MDM2 among 64 amplified genes. MDM2 amplification is a diagnostic hallmark of ALT/WDLPS/DDLPS. In adult cases, it is typically located in ring or giant marker chromosomes. In the present case, extra-copies of MDM2 were located on double minute chromosomes (dmin). This raised the hypothesis of dmin being precursors of adult's rings and giant markers and may provide indications for a better understanding of the mechanisms of adipose tumor oncogenesis.

Keywords: atypical lipomatous tumor; dedifferentiated liposarcoma; double minute chromosome; pediatric; well-differentiated liposarcoma.

Publication types

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

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Child
  • Chromosomes, Human, Pair 12 / genetics
  • Female
  • Gene Amplification*
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / pathology
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2