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dc.contributor.authorCorreia, Lizelle
dc.contributor.authorMagno, Ramiro
dc.contributor.authorXavier, Joana M
dc.contributor.authorde Almeida, Bernardo P
dc.contributor.authorDuarte, Isabel
dc.contributor.authorEsteves, Filipa
dc.contributor.authorGhezzo, Marinella
dc.contributor.authorEldridge, Matthew
dc.contributor.authorSun, Chong
dc.contributor.authorBosma, Astrid
dc.contributor.authorMittempergher, Lorenza
dc.contributor.authorMarreiros, Ana
dc.contributor.authorBernards, Rene
dc.contributor.authorCaldas, Carlos
dc.contributor.authorChin, Suet-Feung
dc.contributor.authorMaia, Ana-Teresa
dc.date.accessioned2022-06-08T15:01:04Z
dc.date.available2022-06-08T15:01:04Z
dc.date.issued2022-06-08
dc.date.submitted2021-06-02
dc.identifier.issn2374-4677
dc.identifier.others41523-022-00435-9
dc.identifier.other435
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337906
dc.descriptionFunder: EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011264; Grant(s): FP7/2007-2013/303745
dc.descriptionFunder: FCT-Fundação para a Ciência e a Tecnologia, and CRESC ALGARVE 2020: ALG-01-0145-FEDER-31477 – “DevoCancer”, CBMR - UID/BIM/04773/2013, POCI-01-0145-FEDER-022184 - ”GenomePT”. Maratona da Saúde Award
dc.descriptionFunder: Fundação para a Ciência e Tecnologia: DL 57/2016/CP1361/CT0042, SFRH/BPD/99502/2014
dc.descriptionFunder: Fundação para a Ciência e Tecnologia: PD/BD/114252/2016
dc.description.abstractPIK3CA 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/67/1347
dc.subject/692/308/575
dc.subjectarticle
dc.titleAllelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant.
dc.typeArticle
dc.date.updated2022-06-08T15:01:04Z
prism.issueIdentifier1
prism.publicationNameNPJ Breast Cancer
prism.volume8
dc.identifier.doi10.17863/CAM.85313
dcterms.dateAccepted2022-03-31
rioxxterms.versionofrecord10.1038/s41523-022-00435-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCorreia, Lizelle [0000-0003-2184-9962]
dc.contributor.orcidEldridge, Matthew [0000-0002-5799-8911]
dc.contributor.orcidSun, Chong [0000-0001-9008-2158]
dc.contributor.orcidMarreiros, Ana [0000-0001-9410-4772]
dc.contributor.orcidBernards, Rene [0000-0001-8677-3423]
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.contributor.orcidChin, Suet-Feung [0000-0001-5697-1082]
dc.contributor.orcidMaia, Ana-Teresa [0000-0002-0454-9207]
dc.identifier.eissn2374-4677
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idCancer Research UK (A16942)
cam.issuedOnline2022-06-08


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