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This syndrome is characterized by more severe symptoms than those shown by patients with intragenic\n                    <jats:italic>NF1<\/jats:italic>\n                    mutation and by variable expressivity, which is not fully explained by the haploinsufficiency of the genes included in the deletions. We here reevaluate an 8-year-old NF1 patient, who carries an atypical deletion generating the\n                    <jats:italic>RNF135-SUZ12<\/jats:italic>\n                    chimeric gene, previously described when he was 3 years old. As the patient has developed multiple cutaneous\/subcutaneous neurofibromas over the past 5 years, we hypothesized a role of\n                    <jats:italic>RNF135-SUZ12<\/jats:italic>\n                    chimeric gene in the onset of the patient\u2019s tumor phenotype. Interestingly,\n                    <jats:italic>SUZ12<\/jats:italic>\n                    is generally lost or disrupted in NF1 microdeletion syndrome and frequently associated to cancer as\n                    <jats:italic>RNF135.<\/jats:italic>\n                    Expression analysis confirmed the presence of the chimeric gene transcript and revealed hypo-expression of five out of the seven analyzed target genes of the polycomb repressive complex 2 (PRC2), to which SUZ12 belongs, in the patient\u2019s peripheral blood, indicating a higher transcriptional repression activity mediated by PRC2. Furthermore, decreased expression of tumor suppressor gene\n                    <jats:italic>TP53<\/jats:italic>\n                    , which is targeted by RNF135, was detected. These results suggest that RNF135-SUZ12 chimera may acquire a gain of function, compared with SUZ12 wild type in the PRC2 complex, and a loss of function relative to RNF135 wild type. Both events may have a role in the early onset of the patient\u2019s neurofibromas.\n                  <\/jats:p>","DOI":"10.1007\/s10048-023-00718-8","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T01:01:45Z","timestamp":1683248505000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deregulated expression of polycomb repressive complex 2 target genes in a NF1 patient with microdeletion generating the RNF135-SUZ12 chimeric gene"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-8376","authenticated-orcid":false,"given":"Viviana","family":"Tritto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Grilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-8514","authenticated-orcid":false,"given":"Donatella","family":"Milani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-8467","authenticated-orcid":false,"given":"Paola","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"718_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1002\/humu.10299","volume":"23","author":"L Kluwe","year":"2004","unstructured":"Kluwe L, Siebert R, Gesk S et al (2004) Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene. 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The study is going to be approved by the Ethics Committee of the Ca\u2019 Granda Ospedale Maggiore Policlinico di Milano, Italy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}