Abstract
Background
The term “intramuscular hemangioma capillary type” (IHCT) refers to a fast-flow vascular lesion that is classified as a tumor, although its phenotype overlaps with arteriovenous malformation (AVM). The purpose of this study was to identify somatic mutations in IHCT.
Methods
Affected tissue specimens were obtained during a clinically indicated procedure. The diagnosis of IHCT was based on history, physical examination, imaging and histopathology. Because somatic mutations in cancer-associated genes can cause vascular malformations, we sequenced exons from 446 cancer-related genes in DNA from 7 IHCT specimens. We then performed mutation-specific droplet digital PCR (ddPCR) to independently test for the presence of a somatic mutation found by sequencing and to screen one additional IHCT sample.
Results
We detected somatic mutations in 6 of 8 IHCT specimens. Four specimens had a mutation in MAP2K1 (p.Q58_E62del, p.P105_I107delinsL, p.Q56P) and 2 specimens had mutations in KRAS (p.K5E and p.G12D, p.G12D and p.Q22R). Mutant allele frequencies detected by sequencing and confirmed by ddPCR ranged from 2 to 15%.
Conclusions
IHCT lesions are phenotypically similar to AVMs and contain the same somatic MAP2K1 or KRAS mutations, suggesting that IHCT is on the AVM spectrum. We propose calling this lesion “intramuscular fast-flow vascular anomaly.”
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Acknowledgements
We thank Profile at Brigham and Women’s Hospital and Dana-Farber Cancer Institute (DFCI), and the Center for Cancer Genome Discovery (CCGD) at the DFCI for their assistance in analyzing the sequencing data. The authors also thank Dr. Steven Hann for his scientific expertise. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD093735 (AKG), the Translational Research Program Boston Children’s Hospital (AKG) and the National Institutes of Health under Award Number NIH R01AR064231 (MLW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Goss, J.A., Konczyk, D.J., Smits, P.J. et al. Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations. Angiogenesis 22, 547–552 (2019). https://doi.org/10.1007/s10456-019-09678-w
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DOI: https://doi.org/10.1007/s10456-019-09678-w