Jansen Philipp, Müller Hansgeorg, Lodde Georg C, Zaremba Anne, Möller Inga, Sucker Antje, Paschen Annette, Esser Stefan, Schaller Jörg, Gunzer Matthias, Standl Fabian, Bauer Sebastian, Schadendorf Dirk, Mentzel Thomas, Hadaschik Eva, Griewank Klaus G
Department of Dermatology, University Hospital Essen, University Duisburg-Essen and German Cancer Consortium (DKTK), Essen, Germany.
Dermatohistologie am Stachus, Munich, Germany.
Front Genet. 2021 Apr 30;12:663272. doi: 10.3389/fgene.2021.663272. eCollection 2021.
Cutaneous vascular tumors consist of a heterogeneous group of benign proliferations, including a range of hemangiomas and vascular malformations, as well as heterogeneous groups of both borderline and malignant neoplasms such as Kaposi's sarcoma and angiosarcomas. The genetics of these tumors have been assessed independently in smaller individual cohorts making comparisons difficult. In our study, we analyzed a representative cohort of benign vascular proliferations observed in a clinical routine setting as well as a selection of malignant vascular proliferations. Our cohort of 104 vascular proliferations including hemangiomas, malformations, angiosarcomas and Kaposi's sarcoma were screened by targeted next-generation sequencing for activating genetic mutations known or assumed to be potentially relevant in vascular proliferations. An association analysis was performed for mutation status and clinico-pathological parameters. Frequent activating hotspot mutations in genes, including Q205, and Q209 were identified in 16 of 64 benign vascular tumors (25%). gene mutations were particularly frequent (52%) in cherry (senile) hemangiomas (13 of 25). In angiosarcomas, activating mutations ( and ) were identified in three samples (16%). No activating or gene mutations were identified in Kaposi's sarcomas. Our study identifies Q205, and Q209 mutations as being the most common and mutually exclusive mutations in benign hemangiomas. These mutations were not identified in malignant vascular tumors, which could be of potential diagnostic value in distinguishing these entities.
皮肤血管肿瘤由一组异质性的良性增殖性病变组成，包括一系列血管瘤和血管畸形，以及一些交界性和恶性肿瘤的异质性群体，如卡波西肉瘤和血管肉瘤。这些肿瘤的遗传学在较小的个体队列中独立评估，使得比较变得困难。在我们的研究中，我们分析了在临床常规环境中观察到的一组具有代表性的良性血管增殖性病变以及一些恶性血管增殖性病变。我们的104例血管增殖性病变队列，包括血管瘤、血管畸形、血管肉瘤和卡波西肉瘤，通过靶向二代测序筛选已知或假定与血管增殖可能相关的激活基因突变。对突变状态和临床病理参数进行了关联分析。在64例良性血管肿瘤中的16例（25%）中发现了基因中的频繁激活热点突变，包括Q205、和Q209。基因突变在樱桃（老年性）血管瘤（25例中的13例）中尤为常见（52%）。在血管肉瘤中，在三个样本（16%）中发现了激活突变（和）。在卡波西肉瘤中未发现激活或基因突变。我们的研究确定Q205、和Q209突变是良性血管瘤中最常见且相互排斥的突变。在恶性血管肿瘤中未发现这些突变，这可能对区分这些实体具有潜在的诊断价值。
