Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases

Genes Chromosomes Cancer. 2017 Dec;56(12):855-860. doi: 10.1002/gcc.22501. Epub 2017 Sep 23.

Abstract

Spindle cell hemangioma (SCH) is a distinct vascular soft-tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP)-based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Female
  • Hemangioma / genetics*
  • Hemangioma / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology

Substances

  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human