Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis

Autores
Pavicic, Walter Hernan; Nieminen, Taina; Gylling, Annette; Pursiheimo, Juha Pekka; Laiho, Asta; Gyenesei, Attila; Järvinen, Heikki J.; Peltomäki, Paivi
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation-negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation-dependent probe amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger sequencing of promoter regions. A novel 132-kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele-specific APC expression. No promoter-specific point mutations or hypermethylation were present in any family. In conclusion, promoter-specific alterations are a rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele-specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations.
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. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. University of Helsinki. Helsinki; Finlandia
Fil: Nieminen, Taina. University of Helsinki. Helsinki; Finlandia
Fil: Gylling, Annette. University of Helsinki. Helsinki; Finlandia
Fil: Pursiheimo, Juha Pekka. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Laiho, Asta. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Gyenesei, Attila. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Järvinen, Heikki J.. Helsinki University Central Hospital. Helsinki; Finlandia
Fil: Peltomäki, Paivi. University of Helsinki. Helsinki; Finlandia
Materia
Apc
Familial Adenomatous Polyposis
Promoter
Deletion
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:11336/33221
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/33221
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposisPavicic, Walter HernanNieminen, TainaGylling, AnnettePursiheimo, Juha PekkaLaiho, AstaGyenesei, AttilaJärvinen, Heikki J.Peltomäki, PaiviApcFamilial Adenomatous PolyposisPromoterDeletionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation-negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation-dependent probe amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger sequencing of promoter regions. A novel 132-kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele-specific APC expression. No promoter-specific point mutations or hypermethylation were present in any family. In conclusion, promoter-specific alterations are a rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele-specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations.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. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. University of Helsinki. Helsinki; FinlandiaFil: Nieminen, Taina. University of Helsinki. Helsinki; FinlandiaFil: Gylling, Annette. University of Helsinki. Helsinki; FinlandiaFil: Pursiheimo, Juha Pekka. University of Turku and Åbo Akademi University. Turku; FinlandiaFil: Laiho, Asta. University of Turku and Åbo Akademi University. Turku; FinlandiaFil: Gyenesei, Attila. University of Turku and Åbo Akademi University. Turku; FinlandiaFil: Järvinen, Heikki J.. Helsinki University Central Hospital. Helsinki; FinlandiaFil: Peltomäki, Paivi. University of Helsinki. Helsinki; FinlandiaWiley-liss, Div John Wiley & Sons Inc2014-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33221Peltomäki, Paivi; Gyenesei, Attila; Pursiheimo, Juha Pekka; Järvinen, Heikki J.; Laiho, Asta; Gylling, Annette; et al.; Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 53; 10; 6-2014; 857-8641045-2257CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/gcc.22197info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/gcc.22197/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:03Zoai:ri.conicet.gov.ar:11336/33221instacron: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:34982025-09-29 09:56:04.017CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
title Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
spellingShingle Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
Pavicic, Walter Hernan
Apc
Familial Adenomatous Polyposis
Promoter
Deletion
title_short Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
title_full Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
title_fullStr Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
title_full_unstemmed Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
title_sort Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis
dc.creator.none.fl_str_mv Pavicic, Walter Hernan
Nieminen, Taina
Gylling, Annette
Pursiheimo, Juha Pekka
Laiho, Asta
Gyenesei, Attila
Järvinen, Heikki J.
Peltomäki, Paivi
author Pavicic, Walter Hernan
author_facet Pavicic, Walter Hernan
Nieminen, Taina
Gylling, Annette
Pursiheimo, Juha Pekka
Laiho, Asta
Gyenesei, Attila
Järvinen, Heikki J.
Peltomäki, Paivi
author_role author
author2 Nieminen, Taina
Gylling, Annette
Pursiheimo, Juha Pekka
Laiho, Asta
Gyenesei, Attila
Järvinen, Heikki J.
Peltomäki, Paivi
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apc
Familial Adenomatous Polyposis
Promoter
Deletion
topic Apc
Familial Adenomatous Polyposis
Promoter
Deletion
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation-negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation-dependent probe amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger sequencing of promoter regions. A novel 132-kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele-specific APC expression. No promoter-specific point mutations or hypermethylation were present in any family. In conclusion, promoter-specific alterations are a rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele-specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations.
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. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. University of Helsinki. Helsinki; Finlandia
Fil: Nieminen, Taina. University of Helsinki. Helsinki; Finlandia
Fil: Gylling, Annette. University of Helsinki. Helsinki; Finlandia
Fil: Pursiheimo, Juha Pekka. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Laiho, Asta. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Gyenesei, Attila. University of Turku and Åbo Akademi University. Turku; Finlandia
Fil: Järvinen, Heikki J.. Helsinki University Central Hospital. Helsinki; Finlandia
Fil: Peltomäki, Paivi. University of Helsinki. Helsinki; Finlandia
description In familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation-negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation-dependent probe amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger sequencing of promoter regions. A novel 132-kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele-specific APC expression. No promoter-specific point mutations or hypermethylation were present in any family. In conclusion, promoter-specific alterations are a rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele-specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations.
publishDate 2014
dc.date.none.fl_str_mv 2014-06
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/11336/33221
Peltomäki, Paivi; Gyenesei, Attila; Pursiheimo, Juha Pekka; Järvinen, Heikki J.; Laiho, Asta; Gylling, Annette; et al.; Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 53; 10; 6-2014; 857-864
1045-2257
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33221
identifier_str_mv Peltomäki, Paivi; Gyenesei, Attila; Pursiheimo, Juha Pekka; Järvinen, Heikki J.; Laiho, Asta; Gylling, Annette; et al.; Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 53; 10; 6-2014; 857-864
1045-2257
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/gcc.22197
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/gcc.22197/abstract
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
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
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 13.070432

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