Mutational analysis using Sanger and Next Generation Sequencing in sporadic spindle cell hemangiomas: A study of 19 cases

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 in order to compare their diagnostic value. Four out of ten cases tested by Sanger sequencing and one of the two cases analyzed using MLPA revealed a mutation in IDH1 (p.R132C). The seven remaining negative cases and additional six cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (eight cases) and IDH2 (three cases; twice p.R172S and once p.R172G, respectively). One case was negative. Due to insufficient DNA quality and insufficient coverage, two 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. This article is protected by copyright. All rights reserved.

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