{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:04:40Z","timestamp":1790885080901,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"publisher","award":["21790"],"award-info":[{"award-number":["21790"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007514","name":"University of Pisa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003197","name":"AIFA","doi-asserted-by":"publisher","award":["PRA_2022_51"],"award-info":[{"award-number":["PRA_2022_51"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>About 20% of sporadic medullary thyroid carcinomas (MTC) have no RET\/RAS somatic alterations or other known gene alterations. The aim of this study was to investigate RET\/RAS-negative MTC for the presence of NF1 alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 18 sporadic RET\/RAS-negative MTC cases. Next-generation sequencing (NGS) of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene. The effect of NF1 alterations on the transcripts was characterized by reverse transcriptase\u2013polymerase chain reaction (RT\u2013PCR), and the loss of heterozygosity (LOH) of the other NF1 allele was investigated with Multiplex Ligation-dependent Probe Amplification (MLPA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two cases showed biallelic inactivation of NF1 with a prevalence of about 11% of RET\/RAS-negative cases. In a patient affected by neurofibromatosis, there was a somatic intronic point mutation determining the transcript alteration in 1 allele and a germline LOH in the other. In a second patient, we described that both the point mutation and the LOH were somatic events; this latter finding shows, for the first time, a driver role of NF1 inactivation in MTC independent of RET\/RAS alterations and the presence of neurofibromatosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>About 11% of our series of sporadic RET\/RAS-negative MTC harbor biallelic inactivation of the NF1 suppressor gene also regardless of neurofibromatosis status. According to our results, NF1 alterations should be searched in all RET\/RAS-negative MTC as possible drivers. Moreover, this finding reduces the number of negative sporadic MTC and may have important clinical implications in the management of these tumors.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ejendo\/lvad051","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T17:33:17Z","timestamp":1684776797000},"page":"430-437","source":"Crossref","is-referenced-by-count":17,"title":["<i>NF1<\/i>gene inactivation acts as a tumor driver in<i>RET\/RAS<\/i>-negative medullary thyroid carcinomas"],"prefix":"10.1093","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-9343","authenticated-orcid":false,"given":"Raffaele","family":"Ciampi","sequence":"first","affiliation":[{"name":"Unit of Endocrinology, Department of Clinical and Experimental Medicine, University Hospital of Pisa , Via Paradisa, 2, 56124 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ramone","sequence":"additional","affiliation":[{"name":"Unit 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