{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:26:32Z","timestamp":1791354392104,"version":"4.3.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Protection of Telomeres Protein 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex, regulating telomere length. Some\n                    <jats:italic>POT1<\/jats:italic>\n                    gene pathogenic variants (PV) lead to telomere elongation, genomic instability and higher risk of cancer.\n                    <jats:italic>POT1<\/jats:italic>\n                    tumour predisposition syndrome (POT1-TPD) has autosomal dominant inheritance and unknown penetrance. It is associated with increased risk of cutaneous melanoma, chronic lymphocytic leukaemia, angiosarcoma and gliomas. In this work, we aim to describe a broader cancer phenotype related to POT1-TPD, in three families (two with a four generation pedigree, one with a five generation pedigree). The three index cases were referred to our oncogenetic centre for genetic counselling due to their personal history of cancer. Two underwent clinical exome sequencing of 4,867 genes associated with Mendelian genetic diseases, and another underwent gene panel sequencing including\n                    <jats:italic>POT1<\/jats:italic>\n                    , which identified three different\n                    <jats:italic>POT1<\/jats:italic>\n                    PV: NC_000007.14(NM_015450.2):c.349C&gt;T; NC_000007.14(NM_015450.2):c.233T&gt;C and NC_000007.14(NM_015450.2):c.818G&gt;A; already described in the literature. Referenced relatives, did a target genetic test (according to the\n                    <jats:italic>POT1<\/jats:italic>\n                    PV identified in the family). In total, 37 individuals were tested (51.4% females), median age of 46 (22\u201381) years, with\n                    <jats:italic>POT1<\/jats:italic>\n                    PV detected in 22. POT1-TPD was observed, but also a higher incidence of other cancers (other sarcomas, papillary thyroid cancer, early onset prostate cancer and leukaemia). These findings contribute to an increase in our knowledge about\n                    <jats:italic>POT1<\/jats:italic>\n                    PV, and it can play a role in the definition of future\n                    <jats:italic>POT1<\/jats:italic>\n                    PV screening criteria,\n                    <jats:italic>POT1<\/jats:italic>\n                    carrier surveillance protocols (possibly considering screening for all types of sarcomas) and in genetic counselling.\n                  <\/jats:p>","DOI":"10.1038\/s41431-024-01611-0","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T09:08:54Z","timestamp":1717578534000},"page":"980-986","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["POT1 tumour predisposition: a broader spectrum of associated malignancies and proposal for additional screening program"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0383-1419","authenticated-orcid":false,"given":"Marta","family":"Baptista Freitas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Desmyter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Badoer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Smits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-7858","authenticated-orcid":false,"given":"Isabelle","family":"Vandernoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphn\u00e9","family":"t\u00b4Kint de Roodenbeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"1611_CR1","unstructured":"Henry ML Osborne JR, Else T. POT1 Tumor Predisposition. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews\u00ae. Seattle: University of Washington; 2020."},{"key":"1611_CR2","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.3390\/cancers12102739","volume":"12","author":"Y Wu","year":"2020","unstructured":"Wu Y, Poulos RC, Reddel RR. Role of POT1 in Human Cancer. Cancers. 2020;12:2739.","journal-title":"Cancers"},{"key":"1611_CR3","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1002\/jcp.31034","volume":"238","author":"NH Zade","year":"2023","unstructured":"Zade NH, Khattar E. POT1 mutations cause differential effects on telomere length leading to opposing disease phenotypes. J Cell Physiol. 2023;238:1237\u201355.","journal-title":"J Cell Physiol"},{"key":"1611_CR4","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.1056\/NEJMe2303022","volume":"388","author":"G Vassiliou","year":"2023","unstructured":"Vassiliou G. Telomere Length and Clonal Hematopoiesis. N Engl J Med. 2023;388:2481\u20134.","journal-title":"N Engl J Med"},{"key":"1611_CR5","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.gde.2020.02.002","volume":"60","author":"Y Gong","year":"2020","unstructured":"Gong Y, Stock AJ, Liu Y. The enigma of excessively long telomeres in cancer: lessons learned from rare human POT1 variants. Curr Opin Genet Dev. 2020;60:48\u201355.","journal-title":"Curr Opin Genet Dev"},{"key":"1611_CR6","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1056\/NEJMoa2300503","volume":"388","author":"EA DeBoy","year":"2023","unstructured":"DeBoy EA, Tassia MG, Schratz KE, Yan SM, Cosner ZL, McNally EJ, et al. Familial Clonal Hematopoiesis in a Long Telomere Syndrome. 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A written informed consent was obtained from all the individuals involved in this study in accordance with the Declaration of Helsinki, approved by the Ethics Committee of the <i>H\u00f4pital Erasme<\/i>, <i>Universit\u00e9 Libre de Bruxelles<\/i> (reference: Q2015\/003).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}