{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:33:10Z","timestamp":1764646390490,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T00:00:00Z","timestamp":1657929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lateralized\/segmental overgrowth disorders (LOs) encompass a heterogeneous group of congenital conditions with excessive body tissue growth. Documented molecular alterations in LOs mostly consist of somatic variants in genes of the PI3KCA\/AKT\/mTOR pathway or of chromosome band 11p15.5 imprinted region anomalies. In some cases, somatic pathogenic variants in genes of the RAS\/MAPK pathway have been reported. We present the first case of a somatic pathogenic variant (T507K) in<jats:italic>PTPN11<\/jats:italic>causing a LO phenotype characterized by severe lateralized overgrowth, vascular proliferation, and cerebral astrocytoma. The T507K variant was detected in DNA from overgrown tissue in a leg with capillary malformation. The astrocytoma tissue showed a higher<jats:italic>PTPN11<\/jats:italic>variant allele frequency. A pathogenic variant in<jats:italic>FGFR1<\/jats:italic>was also found in tumor tissue, representing a second hit on the RAS\/MAPK pathway. These findings indicate that RAS\/MAPK cascade overactivation can cause mosaic overgrowth phenotypes resembling PIK3CA\u2010related overgrowth disorders (PROS) with cancer predisposition and are consistent with the hypothesis that RAS\/MAPK hyperactivation can be involved in the pathogenesis of astrocytoma. This observation raises the issue of cancer predisposition in patients with RAS\/MAPK pathway gene variants and expands genotype spectrum of LOs and the treatment options for similar cases through inhibition of the RAS\/MAPK oversignaling.<\/jats:p>","DOI":"10.1002\/gcc.23086","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T10:04:35Z","timestamp":1656756275000},"page":"689-695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lateralized overgrowth with vascular malformation caused by a somatic<i>PTPN11<\/i>pathogenic variant: Another piece added to the puzzle of mosaic<scp>RASopathies<\/scp>"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-6013","authenticated-orcid":false,"given":"Alessandro","family":"Mussa","sequence":"first","affiliation":[{"name":"Department of Public Health and Pediatric Sciences University of Torino Torino 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