Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases |
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Authors: | Roel W. ten Broek Elise M. Bekers Wendy W. J. de Leng Eric Strengman Bastiaan B. J. Tops Heinz Kutzner Jan Willem Leeuwis Joost M. van Gorp David H. Creytens Thomas Mentzel Paul J. van Diest Astrid Eijkelenboom Uta Flucke |
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Affiliation: | 1. Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands;2. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands;3. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;4. Dermatopathology Bodensee, Friedrichshafen, Germany;5. Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands;6. Department of Pathology, Diakonessenhuis Utrecht, Utrecht, The Netherlands;7. Department of Pathology, Ghent University Hospital, Ghent University, Ghent, Belgium |
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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. |
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