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

Autores
Olkinuora, Alisa Petriina; Mayordomo, Andrea Constanza; Kauppinen, Anni Katariina; Cerliani, María Belén; Coraglio, Mariana; Collia, Ávila Karina; Gutiérrez, Alejandro; Alvarez, Karin; Cassana, Alessandra; Lopéz Köstner, Francisco; Jauk, Federico; García-Rivello, Hernán; Ristimäki, Ari; Koskenvuo, Laura; Lepistö, Anna; Nieminen, Taina Tuulikki; Vaccaro, Carlos Alberto; Pavicic, Walter Hernan; Peltomäki, Päivi
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>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.
Fil: Olkinuora, Alisa Petriina. University of Helsinki; Finlandia
Fil: Mayordomo, Andrea Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Kauppinen, Anni Katariina. University of Helsinki; Finlandia
Fil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Coraglio, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Collia, Ávila Karina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Gutiérrez, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Alvarez, Karin. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Cassana, Alessandra. Universidad de Los Andes; Chile
Fil: Lopéz Köstner, Francisco. No especifíca;
Fil: Jauk, Federico. Universidad de Los Andes; Chile
Fil: García-Rivello, Hernán. Hospital Italiano; Argentina
Fil: Ristimäki, Ari. Hospital Italiano; Argentina
Fil: Koskenvuo, Laura. University of Helsinki; Finlandia
Fil: Lepistö, Anna. University of Helsinki; Finlandia
Fil: Nieminen, Taina Tuulikki. University of Helsinki; Finlandia
Fil: Vaccaro, Carlos Alberto. University of Helsinki; Finlandia
Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Peltomäki, Päivi. University of Helsinki; Finlandia
Materia
DNA GLYCOSYLASE
EXOME SEQUENCING
GERMLINE VARIANT
MUTYH
NEIL1
NTHL1
OGG1
POLYPOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/210670
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/210670
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continentsOlkinuora, Alisa PetriinaMayordomo, Andrea ConstanzaKauppinen, Anni KatariinaCerliani, María BelénCoraglio, MarianaCollia, Ávila KarinaGutiérrez, AlejandroAlvarez, KarinCassana, AlessandraLopéz Köstner, FranciscoJauk, FedericoGarcía-Rivello, HernánRistimäki, AriKoskenvuo, LauraLepistö, AnnaNieminen, Taina TuulikkiVaccaro, Carlos AlbertoPavicic, Walter HernanPeltomäki, PäiviDNA GLYCOSYLASEEXOME SEQUENCINGGERMLINE VARIANTMUTYHNEIL1NTHL1OGG1POLYPOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Recently, 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>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>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.Fil: Olkinuora, Alisa Petriina. University of Helsinki; FinlandiaFil: Mayordomo, Andrea Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Kauppinen, Anni Katariina. University of Helsinki; FinlandiaFil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Coraglio, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Collia, Ávila Karina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Gutiérrez, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Alvarez, Karin. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Cassana, Alessandra. Universidad de Los Andes; ChileFil: Lopéz Köstner, Francisco. No especifíca;Fil: Jauk, Federico. Universidad de Los Andes; ChileFil: García-Rivello, Hernán. Hospital Italiano; ArgentinaFil: Ristimäki, Ari. Hospital Italiano; ArgentinaFil: Koskenvuo, Laura. University of Helsinki; FinlandiaFil: Lepistö, Anna. University of Helsinki; FinlandiaFil: Nieminen, Taina Tuulikki. University of Helsinki; FinlandiaFil: Vaccaro, Carlos Alberto. University of Helsinki; FinlandiaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Peltomäki, Päivi. University of Helsinki; FinlandiaFrontiers Media2022-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/210670Olkinuora, Alisa Petriina; Mayordomo, Andrea Constanza; Kauppinen, Anni Katariina; Cerliani, María Belén; Coraglio, Mariana; et al.; Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents; Frontiers Media; Frontiers in Oncology; 12; 10-2022; 1-132234-943XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.870863/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.870863info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:05Zoai:ri.conicet.gov.ar:11336/210670instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:05.487CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
title Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
spellingShingle Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
Olkinuora, Alisa Petriina
DNA GLYCOSYLASE
EXOME SEQUENCING
GERMLINE VARIANT
MUTYH
NEIL1
NTHL1
OGG1
POLYPOSIS
title_short Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
title_full Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
title_fullStr Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
title_full_unstemmed Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
title_sort Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
dc.creator.none.fl_str_mv Olkinuora, Alisa Petriina
Mayordomo, Andrea Constanza
Kauppinen, Anni Katariina
Cerliani, María Belén
Coraglio, Mariana
Collia, Ávila Karina
Gutiérrez, Alejandro
Alvarez, Karin
Cassana, Alessandra
Lopéz Köstner, Francisco
Jauk, Federico
García-Rivello, Hernán
Ristimäki, Ari
Koskenvuo, Laura
Lepistö, Anna
Nieminen, Taina Tuulikki
Vaccaro, Carlos Alberto
Pavicic, Walter Hernan
Peltomäki, Päivi
author Olkinuora, Alisa Petriina
author_facet Olkinuora, Alisa Petriina
Mayordomo, Andrea Constanza
Kauppinen, Anni Katariina
Cerliani, María Belén
Coraglio, Mariana
Collia, Ávila Karina
Gutiérrez, Alejandro
Alvarez, Karin
Cassana, Alessandra
Lopéz Köstner, Francisco
Jauk, Federico
García-Rivello, Hernán
Ristimäki, Ari
Koskenvuo, Laura
Lepistö, Anna
Nieminen, Taina Tuulikki
Vaccaro, Carlos Alberto
Pavicic, Walter Hernan
Peltomäki, Päivi
author_role author
author2 Mayordomo, Andrea Constanza
Kauppinen, Anni Katariina
Cerliani, María Belén
Coraglio, Mariana
Collia, Ávila Karina
Gutiérrez, Alejandro
Alvarez, Karin
Cassana, Alessandra
Lopéz Köstner, Francisco
Jauk, Federico
García-Rivello, Hernán
Ristimäki, Ari
Koskenvuo, Laura
Lepistö, Anna
Nieminen, Taina Tuulikki
Vaccaro, Carlos Alberto
Pavicic, Walter Hernan
Peltomäki, Päivi
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA GLYCOSYLASE
EXOME SEQUENCING
GERMLINE VARIANT
MUTYH
NEIL1
NTHL1
OGG1
POLYPOSIS
topic DNA GLYCOSYLASE
EXOME SEQUENCING
GERMLINE VARIANT
MUTYH
NEIL1
NTHL1
OGG1
POLYPOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>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.
Fil: Olkinuora, Alisa Petriina. University of Helsinki; Finlandia
Fil: Mayordomo, Andrea Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Kauppinen, Anni Katariina. University of Helsinki; Finlandia
Fil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Coraglio, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Collia, Ávila Karina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Gutiérrez, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Alvarez, Karin. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Cassana, Alessandra. Universidad de Los Andes; Chile
Fil: Lopéz Köstner, Francisco. No especifíca;
Fil: Jauk, Federico. Universidad de Los Andes; Chile
Fil: García-Rivello, Hernán. Hospital Italiano; Argentina
Fil: Ristimäki, Ari. Hospital Italiano; Argentina
Fil: Koskenvuo, Laura. University of Helsinki; Finlandia
Fil: Lepistö, Anna. University of Helsinki; Finlandia
Fil: Nieminen, Taina Tuulikki. University of Helsinki; Finlandia
Fil: Vaccaro, Carlos Alberto. University of Helsinki; Finlandia
Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Peltomäki, Päivi. University of Helsinki; Finlandia
description 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>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>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.
publishDate 2022
dc.date.none.fl_str_mv 2022-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/210670
Olkinuora, Alisa Petriina; Mayordomo, Andrea Constanza; Kauppinen, Anni Katariina; Cerliani, María Belén; Coraglio, Mariana; et al.; Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents; Frontiers Media; Frontiers in Oncology; 12; 10-2022; 1-13
2234-943X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/210670
identifier_str_mv Olkinuora, Alisa Petriina; Mayordomo, Andrea Constanza; Kauppinen, Anni Katariina; Cerliani, María Belén; Coraglio, Mariana; et al.; Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents; Frontiers Media; Frontiers in Oncology; 12; 10-2022; 1-13
2234-943X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.870863/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.870863
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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