{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T18:37:18Z","timestamp":1784745438741,"version":"3.55.0"},"reference-count":75,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007287","name":"Worldwide Cancer Research","doi-asserted-by":"publisher","award":["15-1144"],"award-info":[{"award-number":["15-1144"]}],"id":[{"id":"10.13039\/501100007287","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU H2020 Marie Curie project TRANSMIT","award":["GA 722605"],"award-info":[{"award-number":["GA 722605"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>While somatic disruptive mitochondrial DNA (mtDNA) mutations that severely affect the respiratory chain are counter-selected in most human neoplasms, they are the genetic hallmark of indolent oncocytomas, where they appear to contribute to reduce tumorigenic potential. A correlation between mtDNA mutation type and load, and the clinical outcome of a tumor, corroborated by functional studies, is currently lacking. Recurrent familial oncocytomas are extremely rare entities, and they offer the chance to investigate the determinants of oncocytic transformation and the role of both germline and somatic mtDNA mutations in cancer. We here report the first family with Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome showing the inherited predisposition of four individuals to develop parathyroid oncocytic tumors. MtDNA sequencing revealed a rare ribosomal RNA mutation in the germline of all HPT-JT affected individuals whose pathogenicity was functionally evaluated via cybridization technique, and which was counter-selected in the most aggressive infiltrating carcinoma, but positively selected in adenomas. In all tumors different somatic mutations accumulated on this genetic background, with an inverse clear-cut correlation between the load of pathogenic mtDNA mutations and the indolent behavior of neoplasms, highlighting the importance of the former both as modifiers of cancer fate and as prognostic markers.<\/jats:p>","DOI":"10.3390\/cells10112920","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:50:28Z","timestamp":1635465028000},"page":"2920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pathogenic Mitochondrial DNA Mutation Load Inversely Correlates with Malignant Features in Familial Oncocytic Parathyroid Tumors Associated with Hyperparathyroidism-Jaw Tumor Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3486-3985","authenticated-orcid":false,"given":"Monica","family":"De Luise","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6804-7302","authenticated-orcid":false,"given":"Luisa","family":"Iommarini","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"},{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Marchio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-6639","authenticated-orcid":false,"given":"Camelia Alexandra","family":"Coad\u0103","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Repaci","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Turchetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Division of Medical Genetics, IRCSS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lucia","family":"Tardio","sequence":"additional","affiliation":[{"name":"Unit of Pathology, IRCCS S.Orsola University Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzio","family":"Salfi","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Giannina Gaslini Children\u2019s Research Hospital, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Kurelac","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Porcelli","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"},{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy"},{"name":"Interdepartmental Center of Industrial Research (CIRI) Life Science and Health Technologies, University of Bologna, 40064 Ozzano dell\u2019Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gasparre","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e02935","DOI":"10.7554\/eLife.02935","article-title":"Origins and Functional Consequences of Somatic Mitochondrial DNA Mutations in Human 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