Multigene panel testing increases the number of loci associated with gastric cancer predisposition
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/137933 |
Resumo: | The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Multigene panel testing increases the number of loci associated with gastric cancer predispositionCancer predispositionCDH1 geneNext-generation sequencingStomach neoplasmsThe main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition.MDPI20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/137933eng2072-669410.3390/cancers11091340Tedaldi, GPirini, FTebaldi, MZampiga, VCangini, IDanesi, RArcangeli, VRavegnani, MKhouzam, RAMolinari, COliveira, CMorgagni, PSaragoni, LBencivenga, MUlivi, PAmadori, DMartinelli, GFalcini, FRanzani, GNCalistri, Dinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T14:54:14Zoai:repositorio-aberto.up.pt:10216/137933Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:11:15.882753Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
title |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
spellingShingle |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition Tedaldi, G Cancer predisposition CDH1 gene Next-generation sequencing Stomach neoplasms |
title_short |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
title_full |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
title_fullStr |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
title_full_unstemmed |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
title_sort |
Multigene panel testing increases the number of loci associated with gastric cancer predisposition |
author |
Tedaldi, G |
author_facet |
Tedaldi, G Pirini, F Tebaldi, M Zampiga, V Cangini, I Danesi, R Arcangeli, V Ravegnani, M Khouzam, RA Molinari, C Oliveira, C Morgagni, P Saragoni, L Bencivenga, M Ulivi, P Amadori, D Martinelli, G Falcini, F Ranzani, GN Calistri, D |
author_role |
author |
author2 |
Pirini, F Tebaldi, M Zampiga, V Cangini, I Danesi, R Arcangeli, V Ravegnani, M Khouzam, RA Molinari, C Oliveira, C Morgagni, P Saragoni, L Bencivenga, M Ulivi, P Amadori, D Martinelli, G Falcini, F Ranzani, GN Calistri, D |
author2_role |
author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Tedaldi, G Pirini, F Tebaldi, M Zampiga, V Cangini, I Danesi, R Arcangeli, V Ravegnani, M Khouzam, RA Molinari, C Oliveira, C Morgagni, P Saragoni, L Bencivenga, M Ulivi, P Amadori, D Martinelli, G Falcini, F Ranzani, GN Calistri, D |
dc.subject.por.fl_str_mv |
Cancer predisposition CDH1 gene Next-generation sequencing Stomach neoplasms |
topic |
Cancer predisposition CDH1 gene Next-generation sequencing Stomach neoplasms |
description |
The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/137933 |
url |
https://hdl.handle.net/10216/137933 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2072-6694 10.3390/cancers11091340 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799136035929587712 |