Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

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dc.coverageDOI: 10.3389/fonc.2022.870863
dc.creatorOlkinuora, Alisa Petriina
dc.creatorMayordomo, Andrea Constanza
dc.creatorKauppinen, Anni Katariina
dc.creatorCerliani, María Belén
dc.creatorCoraglio, Mariana
dc.creatorCollia, Ávila Karina
dc.creatorGutiérrez, Alejandro
dc.creatorAlvarez, Karin
dc.creatorCassana, Alessandra
dc.creatorLopéz-Köstner, Francisco
dc.creatorJauk, Federico
dc.creatorGarcía-Rivello, Hernán
dc.creatorRistimäki, Ari
dc.creatorKoskenvuo, Laura
dc.creatorLepistö, Anna
dc.creatorNieminen, Taina Tuulikki
dc.creatorVaccaro, Carlos Alberto
dc.creatorPavicic, Walter Hernán
dc.creatorPeltomäki, Päivi
dc.date2022
dc.date.accessioned2025-11-18T19:52:24Z
dc.date.available2025-11-18T19:52:24Z
dc.description<p>Recently, biallelic germline variants of the DNA glycosylase genes MUTYH and NTHL1 were linked to polyposis susceptibility. Significant fractions remain without a molecular explanation, warranting searches for underlying causes. We used exome sequencing to investigate clinically well-defined adenomatous polyposis cases and families from Finland (N=34), Chile (N=21), and Argentina (N=12), all with known susceptibility genes excluded. Nine index cases (13%) revealed germline variants with proven or possible pathogenicity in the DNA glycosylase genes, involving NEIL1 (mono- or biallelic) in 3 cases, MUTYH (monoallelic) in 3 cases, NTHL1 (biallelic) in 1 case, and OGG1 (monoallelic) in 2 cases. NTHL1 was affected with the well-established, pathogenic c.268C&gt;T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G&gt;A, p.(Gly169Asp) variant was observed in two families. In a Finnish family, the variant occurred in trans with a truncating NEIL1 variant (c.821delT). In an Argentine family, the variant co-occurred with a genomic deletion of exons 2 – 11 of PMS2. Mutational signatures in tumor tissues complied with biological functions reported for NEIL1. Our results suggest that germline variants in DNA glycosylase genes may occur in a non-negligible proportion of unexplained colon polyposis cases and may predispose to tumor development.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/318dd5cc-435d-4fd3-981c-9ba7caf69716
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/57701
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.12 (2022) date: 2022-10-28
dc.subjectDNA glycosylase
dc.subjectexome sequencing
dc.subjectgermline variant
dc.subjectMUTYH
dc.subjectNEIL1
dc.subjectNTHL1
dc.subjectOGG1
dc.subjectpolyposis
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continentseng
dc.typeArticleeng
dc.typeArtículospa
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