Genetic heterogeneity in leiomyomas of deep soft tissue

Oncotarget. 2017 Jul 25;8(30):48769-48781. doi: 10.18632/oncotarget.17953.

Abstract

Leiomyoma of deep soft tissue is a rare type of benign smooth muscle tumor that mostly occurs in the retroperitoneum or abdominal cavity of women, and about which very little genetic information exists. In the present study, eight leiomyomas of deep soft tissue were genetically analyzed. G-banding showed that three tumors carried rearrangements of the long arm of chromosome 12, three others had 8q rearrangements, the 7th tumor had deletion of the long arm of chromosome 7, del(7)(q22), and the 8th had aberrations of chromosome bands 3q21~23 and 11q21~22. The target genes of the 12q and 8q aberrations were HMGA2 and PLAG1, respectively. In the leiomyomas with 12q rearrangements, both HMGA2 and PLAG1 were expressed whereas in the tumors with 8q aberrations, only PLAG1 was expressed. In the cases without 12q or 8q aberrations, the expression of HMGA2 was very low and PLAG1 was expressed only in the case with del(7)(q22). All eight leiomyomas of deep soft tissue expressed MED12 but none of them had mutation in exon 2 of that gene. In two tumors with 12q rearrangements, RPSAP52 on 12q14.3 was fused with non-coding RNA (accession number XR_944195) from 14q32.2 or ZFP36L1 from14q24.1. In a tumor with inv(12), exon 3 of HMGA2 was fused to a sequence in intron 1 of the CRADD gene from 12q22. The present data together with those of our two previous studies in which the fusions KAT6B-KANSL1 and EWSR1-PBX3 were described in two retroperitoneal leiomyomas carrying a t(10;17)(q22;q21) and a t(9;22)(q33;q12) translocation, respectively, show that leiomyomas of deep soft tissue are genetically heterogenous but have marked similarities to uterine leiomyomas.

Keywords: HMGA2; PLAG1; cytogenetics; leiomyoma of deep soft tissue.

MeSH terms

  • Adult
  • Aged
  • Chromosome Aberrations
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Exons
  • Female
  • Gene Expression
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease*
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leiomyoma / genetics*
  • Leiomyoma / metabolism
  • Leiomyoma / pathology
  • Middle Aged
  • Mutation
  • Translocation, Genetic

Substances

  • DNA-Binding Proteins
  • HMGA2 Protein
  • PLAG1 protein, human