Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms

in Endocrine-Related Cancer
Authors:
Rachel Pimenta Riechelmann Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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https://orcid.org/0000-0002-0107-9617
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Mauro Daniel Spina Donadio Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Victor Hugo Fonseca de Jesus Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Nathalia de Angelis de Carvalho Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil

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https://orcid.org/0000-0001-6114-7223
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Karina Miranda Santiago Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil

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Milton J Barros Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Laura Lopes Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil

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Gabriel Oliveira dos Santos Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil

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Maria Nirvana Formiga Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil
Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, Brazil

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Dirce Maria Carraro Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil
National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), São Paulo, Brazil

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Giovana Tardin Torrezan Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil
National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), São Paulo, Brazil

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https://orcid.org/0000-0002-8659-5329

Correspondence should be addressed to G T Torrezan: giovana.torrezan@accamargo.org.br
DOI:
https://doi.org/10.1530/ERC-22-0258
Volume/Issue:
Volume 30: Issue 6
Article Type:
Research Article
Article ID:
e220258
Online Publication Date:
11 May 2023
Copyright:
© the author(s) 2023
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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 (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-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.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e220258
Received Date:
02 Mar 2023
Accepted Date:
22 Mar 2023
Print Publication Date:
01 Jun 2023
Online Publication Date:
11 May 2023
Keywords:
germline variants; neuroendocrine tumours; cancer predisposing genes

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