{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:13Z","timestamp":1790627053354,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The commonest tumors associated with neurofibromatosis type 1 (NF1) are benign peripheral nerve sheath tumors, called neurofibromas. Malignant transformation of neurofibromas into aggressive MPNSTs may occur with a poor patient prognosis. A cooperative role of <jats:italic>SUZ12<\/jats:italic> or <jats:italic>EED<\/jats:italic> inactivation, along with <jats:italic>NF1, TP53,<\/jats:italic> and <jats:italic>CDKN2A<\/jats:italic> loss\u2010of\u2010function, has been proposed to drive progression to MPNSTs. An exome sequencing analysis of eight MPNSTs, one plexiform neurofibroma, and seven cutaneous neurofibromas was undertaken. Biallelic inactivation of the <jats:italic>NF1<\/jats:italic> gene was observed in the plexiform neurofibroma and the MPNSTs, underlining that somatic biallelic <jats:italic>NF1<\/jats:italic> inactivation is likely to be the initiating event for plexiform neurofibroma genesis, although it is unlikely to be sufficient for the subsequent MPNST development. The majority (5\/8) of MPNSTs in our analyses demonstrated homozygous or heterozygous deletions of <jats:italic>CDKN2A<\/jats:italic>, which may represent an early event following <jats:italic>NF1<\/jats:italic> LOH in the malignant transformation of Schwann cells from plexiform neurofibroma to MPNST. Biallelic somatic alterations of <jats:italic>SUZ12<\/jats:italic> was also found in 4\/8 MPNSTs. <jats:italic>EED<\/jats:italic> biallelic alterations were detected in 2 of the other four MPNSTs, with one tumor having a homozygous <jats:italic>EED<\/jats:italic> deletion. A missense mutation in the chromatin regulator <jats:italic>KDM2B<\/jats:italic> was also identified in one MPNST. No <jats:italic>TP53<\/jats:italic> point mutations were found in this study, confirming previous data that <jats:italic>TP53<\/jats:italic> mutations may be relatively rare in NF1\u2010associated MPNSTs. Our study confirms the frequent biallelic inactivation of PRC2 subunits <jats:italic>SUZ12<\/jats:italic> and <jats:italic>EED<\/jats:italic> in MPNSTs, and suggests the implication of <jats:italic>KDM2B<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/gcc.22446","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T01:19:35Z","timestamp":1485393575000},"page":"421-426","source":"Crossref","is-referenced-by-count":59,"title":["Confirmation of mutation landscape of NF1\u2010associated malignant peripheral nerve sheath tumors"],"prefix":"10.1002","volume":"56","author":[{"given":"Pierre","family":"Sohier","sequence":"first","affiliation":[{"name":"Service de Pathologie, H\u00f4pital Cochin, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armelle","family":"Luscan","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, 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