{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:14:41Z","timestamp":1790615681306,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">We aimed to correlate alterations in the rat sarcoma virus (RAS)\/mitogen\u2010activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS\/mitogen\u2010activated 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\u2010five 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\u2010Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen\u2010activated protein kinase kinase 1 (n=5). Patients with\n                      <jats:italic>RAS<\/jats:italic>\n                      PVs had advanced disease stages according to the Schobinger classification (stage 3\u20134:\n                      <jats:italic>RAS<\/jats:italic>\n                      , 9\/13 versus non\u2010\n                      <jats:italic>RAS<\/jats:italic>\n                      , 3\/11) and more frequent progression after treatment (\n                      <jats:italic>RAS<\/jats:italic>\n                      , 10\/13 versus non\u2010\n                      <jats:italic>RAS<\/jats:italic>\n                      , 2\/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other\n                      <jats:italic>RAS<\/jats:italic>\n                      PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8\/10 versus other PVs, 6\/19).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This comparison of patients with various PVs in genes of the RAS\/MAPK pathway provides potential associations with certain morphological and clinical phenotypes.\n                      <jats:italic>RAS<\/jats:italic>\n                      variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.\n                    <\/jats:p>\n                  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