{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T23:48:07Z","timestamp":1786578487766,"version":"build-2736575974"},"reference-count":34,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,22]]},"abstract":"<jats:p>\n                    Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.084), functioning NEN (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.041), positive family history of cancer (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (\n                    <jats:italic>CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE<\/jats:italic>\n                    and\n                    <jats:italic>SLX4<\/jats:italic>\n                    ), with most GPVs found in\n                    <jats:italic>MUTYH<\/jats:italic>\n                    (four cases). LOH was performed in eight tumours and detected only in an\n                    <jats:italic>SLX4-<\/jats:italic>\n                    positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0258","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T12:56:44Z","timestamp":1679489804000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":13,"title":["Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms"],"prefix":"10.1530","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-9617","authenticated-orcid":true,"given":"Rachel Pimenta","family":"Riechelmann","sequence":"first","affiliation":[{"name":"Clinical Oncology Department, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Daniel Spina","family":"Donadio","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Hugo Fonseca de","family":"Jesus","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-7223","authenticated-orcid":true,"given":"Nathalia de Angelis","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Clinical and Functional Genomics Group, International Research Center\/CIPE, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Miranda","family":"Santiago","sequence":"additional","affiliation":[{"name":"Clinical and Functional Genomics Group, International Research Center\/CIPE, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton J","family":"Barros","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Pathology, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Oliveira dos Santos","sequence":"additional","affiliation":[{"name":"Department of Pathology, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nirvana Formiga","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"},{"name":"Department of Oncogenetics, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirce Maria","family":"Carraro","sequence":"additional","affiliation":[{"name":"Clinical and Functional Genomics Group, International Research Center\/CIPE, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"},{"name":"National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-5329","authenticated-orcid":true,"given":"Giovana Tardin","family":"Torrezan","sequence":"additional","affiliation":[{"name":"Clinical and Functional Genomics Group, International Research Center\/CIPE, A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"},{"name":"National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Human Molecular Genetics","first-page":"2429","article-title":"WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas","volume":"30","author":"Aavikko","year":"2021","unstructured":"Aavikko MKaasinen EAndersson NPentinmikko NSulo PDonner IPihlajamaa PKuosmanen ABramante SKatainen R, 2021WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas. Human Molecular Genetics302429\u20132440. 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