Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations
Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations
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DOI：
10.1007/s10456-019-09678-w
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发表时间：
2019-11-01
期刊：
影响因子：
9.8
通讯作者：
Greene, Arin K.
中科院分区：
文献类型：
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作者：
Goss, Jeremy A.;Konczyk, Dennis J.;Greene, Arin K.
背景：肌内毛细血管瘤（IHCT）是指一种血流速度较快的血管病变，尽管其表型与动静脉畸形（AVM）重叠，但仍被归类为肿瘤。本研究的目的是确定体细胞突变在IHCT.Methods受影响的组织标本，在临床指征的过程中获得。诊断依据病史、体格检查、影像学及组织病理学。由于癌症相关基因的体细胞突变可导致血管畸形，我们对7份IHCT标本DNA中446个癌症相关基因的外显子进行了测序。然后，我们进行了突变特异性液滴数字PCR（ddPCR），以独立测试测序发现的体细胞突变的存在下，并筛选一个额外的IHCT samples.Results我们检测到体细胞突变的8 IHCT标本中的6。4份标本存在MAP2K1突变（p.Q58_E62del、p.P105_I107delinsL、p.Q56P），2份标本存在KRAS突变（p.K5E和p.G12D、p.G12D和p.Q22R）。结论IHCT与AVM具有相似的表型特征，并含有相同的MAP2K1或KRAS突变，提示IHCT属于AVM。我们建议称这种病变为“肌内快流血管异常”。"
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."