Department of Radiology LMU University Hospital, LMU Munich München Germany.
Interdisziplinäres Zentrum für Gefäßanomalien (IZGA) LMU University Hospital, LMU Munich München Germany.
J Am Heart Assoc. 2024 Apr 16;13(8):e033287. doi: 10.1161/JAHA.123.033287. Epub 2024 Apr 2.
We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification.
This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with PVs had advanced disease stages according to the Schobinger classification (stage 3-4: , 9/13 versus non-, 3/11) and more frequent progression after treatment (, 10/13 versus non-, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19).
This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.
我们旨在将大鼠肉瘤病毒（RAS）/有丝分裂原活化蛋白激酶途径中的改变与血管异常的临床表型相关联，以改善患者和治疗分层。
本回顾性多中心队列研究纳入了 29 名患有颅外血管异常的患者，这些患者的血管异常中存在 RAS/有丝分裂原活化蛋白激酶途径基因的镶嵌性变异（PV）。组织样本是在侵袭性治疗或临床指征活检期间采集的。使用受影响组织的 DNA 通过靶向测序对与血管异常相关的基因进行了 PV 的检测。根据受影响的基因，采用描述性方法对表型特征进行亚组分析。25 例血管畸形、3 例血管肿瘤和 1 例既有血管畸形又有血管肿瘤的患者中存在以下基因的 PV 分布：Kirsten 大鼠肉瘤病毒致癌基因（n=10）、神经母细胞瘤 ras 病毒致癌基因同源物（n=1）、 Harvey 大鼠肉瘤病毒致癌基因同源物（n=5）、V-Raf 鼠肉瘤病毒致癌基因同源物 B（n=8）和丝裂原活化蛋白激酶激酶 1（n=5）。根据 Schobinger 分类，PV 患者的疾病分期更晚（3-4 期：9/13 例比非，3/11 例），治疗后进展更频繁（10/13 例比非，2/11 例）。与其他 PV 相比，具有 Kirsten 大鼠肉瘤病毒致癌基因 PV 的病变侵袭了更多的组织层，包括其他 PV（多个组织层：Kirsten 大鼠肉瘤病毒致癌基因，8/10 例比其他 PV，6/19 例）。
对 RAS/MAPK 途径基因中具有不同 PV 的患者进行比较，为某些形态和临床表型提供了潜在的关联。这些发现为未来更大规模的研究提供了初步数据和假设。
