Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis

Autores
Fundia, Ariela Freya; Cottliar, Alejandra S.; La Motta, Graciela; Crivelli, Adriana; Gómez, Juan Carlos; Slavutsky, Irma Rosa; Larripa, Irene Beatriz
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background and Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. Methods: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). Results: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. Conclusion: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Cottliar, Alejandra S.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: La Motta, Graciela. Hospital San Martin; Argentina
Fil: Crivelli, Adriana. Hospital San Martin; Argentina
Fil: Gómez, Juan Carlos. Hospital San Martin; Argentina
Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Materia
Celiac Disease
Genomic Instability
Loss of Heterozygosis
Microsatellite Instability
Short Tandem Repeats
Tp53 Repeat
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:11336/55971
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55971
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosisFundia, Ariela FreyaCottliar, Alejandra S.La Motta, GracielaCrivelli, AdrianaGómez, Juan CarlosSlavutsky, Irma RosaLarripa, Irene BeatrizCeliac DiseaseGenomic InstabilityLoss of HeterozygosisMicrosatellite InstabilityShort Tandem RepeatsTp53 Repeathttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background and Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. Methods: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). Results: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. Conclusion: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Cottliar, Alejandra S.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: La Motta, Graciela. Hospital San Martin; ArgentinaFil: Crivelli, Adriana. Hospital San Martin; ArgentinaFil: Gómez, Juan Carlos. Hospital San Martin; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaLippincott Williams2008-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55971Fundia, Ariela Freya; Cottliar, Alejandra S.; La Motta, Graciela; Crivelli, Adriana; Gómez, Juan Carlos; et al.; Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis; Lippincott Williams; European Journal Of Gastroenterology & Hepatology; 20; 12; 12-2008; 1159-11660954-691XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/MEG.0b013e3283094ee9info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/crossref?an=00042737-200812000-00005info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:46Zoai:ri.conicet.gov.ar:11336/55971instacron: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 09:52:46.754CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
title Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
spellingShingle Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
Fundia, Ariela Freya
Celiac Disease
Genomic Instability
Loss of Heterozygosis
Microsatellite Instability
Short Tandem Repeats
Tp53 Repeat
title_short Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
title_full Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
title_fullStr Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
title_full_unstemmed Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
title_sort Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis
dc.creator.none.fl_str_mv Fundia, Ariela Freya
Cottliar, Alejandra S.
La Motta, Graciela
Crivelli, Adriana
Gómez, Juan Carlos
Slavutsky, Irma Rosa
Larripa, Irene Beatriz
author Fundia, Ariela Freya
author_facet Fundia, Ariela Freya
Cottliar, Alejandra S.
La Motta, Graciela
Crivelli, Adriana
Gómez, Juan Carlos
Slavutsky, Irma Rosa
Larripa, Irene Beatriz
author_role author
author2 Cottliar, Alejandra S.
La Motta, Graciela
Crivelli, Adriana
Gómez, Juan Carlos
Slavutsky, Irma Rosa
Larripa, Irene Beatriz
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Celiac Disease
Genomic Instability
Loss of Heterozygosis
Microsatellite Instability
Short Tandem Repeats
Tp53 Repeat
topic Celiac Disease
Genomic Instability
Loss of Heterozygosis
Microsatellite Instability
Short Tandem Repeats
Tp53 Repeat
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background and Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. Methods: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). Results: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. Conclusion: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Cottliar, Alejandra S.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: La Motta, Graciela. Hospital San Martin; Argentina
Fil: Crivelli, Adriana. Hospital San Martin; Argentina
Fil: Gómez, Juan Carlos. Hospital San Martin; Argentina
Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
description Background and Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. Methods: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). Results: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. Conclusion: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
publishDate 2008
dc.date.none.fl_str_mv 2008-12
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/11336/55971
Fundia, Ariela Freya; Cottliar, Alejandra S.; La Motta, Graciela; Crivelli, Adriana; Gómez, Juan Carlos; et al.; Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis; Lippincott Williams; European Journal Of Gastroenterology & Hepatology; 20; 12; 12-2008; 1159-1166
0954-691X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55971
identifier_str_mv Fundia, Ariela Freya; Cottliar, Alejandra S.; La Motta, Graciela; Crivelli, Adriana; Gómez, Juan Carlos; et al.; Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis; Lippincott Williams; European Journal Of Gastroenterology & Hepatology; 20; 12; 12-2008; 1159-1166
0954-691X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/MEG.0b013e3283094ee9
info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/crossref?an=00042737-200812000-00005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.13397

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