Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/18536 |
Resumo: | PIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER-, PR-, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer. |
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Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significantPIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER-, PR-, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.ALG-01-0145-FEDER31477POCI-01-0145-FEDER-022184ALG-01-0145-FEDER-30895Nature PortfolioSapientiaCorreia, LizelleMagno, RamiroXavier, JMAlmeida, BernardoDuarte, IsabelEsteves, FilipaGhezzo, MarinellaEldridge, MatthewSun, ChongBosma, AstridMittempergher, LorenzaMarreiros, AnaBernards, ReneCaldas, CarlosChin, Suet-FeungMaia, Ana-Teresa2022-11-23T10:36:08Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/18536eng10.1038/s41523-022-00435-92374-4677info: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:RCAAP2023-07-24T10:30:47Zoai:sapientia.ualg.pt:10400.1/18536Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:08:17.049156Repositório 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 |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
title |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
spellingShingle |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant Correia, Lizelle |
title_short |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
title_full |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
title_fullStr |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
title_full_unstemmed |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
title_sort |
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant |
author |
Correia, Lizelle |
author_facet |
Correia, Lizelle Magno, Ramiro Xavier, JM Almeida, Bernardo Duarte, Isabel Esteves, Filipa Ghezzo, Marinella Eldridge, Matthew Sun, Chong Bosma, Astrid Mittempergher, Lorenza Marreiros, Ana Bernards, Rene Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
author_role |
author |
author2 |
Magno, Ramiro Xavier, JM Almeida, Bernardo Duarte, Isabel Esteves, Filipa Ghezzo, Marinella Eldridge, Matthew Sun, Chong Bosma, Astrid Mittempergher, Lorenza Marreiros, Ana Bernards, Rene Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Correia, Lizelle Magno, Ramiro Xavier, JM Almeida, Bernardo Duarte, Isabel Esteves, Filipa Ghezzo, Marinella Eldridge, Matthew Sun, Chong Bosma, Astrid Mittempergher, Lorenza Marreiros, Ana Bernards, Rene Caldas, Carlos Chin, Suet-Feung Maia, Ana-Teresa |
description |
PIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER-, PR-, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-23T10:36:08Z 2022 2022-01-01T00:00:00Z |
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 |
http://hdl.handle.net/10400.1/18536 |
url |
http://hdl.handle.net/10400.1/18536 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1038/s41523-022-00435-9 2374-4677 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Portfolio |
publisher.none.fl_str_mv |
Nature Portfolio |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133328388915200 |