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Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant

2022Journal article Open Access
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dc.contributor.authorCorreia, Lizelle
dc.contributor.authorMagno, Ramiro
dc.contributor.authorXavier, JM
dc.contributor.authorAlmeida, Bernardo
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.accessioned2022-11-23T10:36:08Z
dc.date.available2022-11-23T10:36:08Z
dc.date.issued2022
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.pt_PT
dc.description.sponsorshipALG-01-0145-FEDER31477; POCI-01-0145-FEDER-022184; ALG-01-0145-FEDER-30895; FP7/2007-2013/303745
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/s41523-022-00435-9pt_PT
dc.identifier.eissn2374-4677
dc.identifier.urihttp://hdl.handle.net/10400.1/18536
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Portfoliopt_PT
dc.relationCentre for Biomedical Research
dc.relationCenter for Health Technology and Services Research
dc.relationNot Available
dc.relationUnveiling cis-regulatory variants role in breast cancer aetiology
dc.relationUnveiling the role of cis-regulatory variation in breast cancer aetiology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleAllelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significantpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Biomedical Research
oaire.awardTitleCenter for Health Technology and Services Research
oaire.awardTitleNot Available
oaire.awardTitleUnveiling cis-regulatory variants role in breast cancer aetiology
oaire.awardTitleUnveiling the role of cis-regulatory variation in breast cancer aetiology
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F04773%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04255%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/DL 57%2F2016/DL 57%2F2016%2FCP1361%2FCT0042/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F99502%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F114252%2F2016/PT
oaire.citation.issue1pt_PT
oaire.citation.titleNPJ Breast Cancerpt_PT
oaire.citation.volume8pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamDL 57/2016
oaire.fundingStreamOE
oaire.fundingStreamOE
person.familyNameCorreia
person.familyNameMagno
person.familyNameGonçalves de Gouveia Maia Xavier
person.familyNameAlmeida
person.familyNamedos Santos Duarte
person.familyNameOleiro Esteves
person.familyNameN Ghezzo
person.familyNameMarreiros
person.familyNameMaia
person.givenNameLizelle
person.givenNameRamiro
person.givenNameJoana
person.givenNameBernardo
person.givenNameGuilhermina Isabel
person.givenNameFilipa Alexandra
person.givenNameMarinella
person.givenNameAna
person.givenNameAna-Teresa
person.identifier1489493
person.identifier.ciencia-idEE13-176A-5613
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person.identifier.ciencia-id9115-8867-D5C9
person.identifier.ciencia-id9A12-9450-7051
person.identifier.orcid0000-0003-2184-9962
person.identifier.orcid0000-0001-5226-3441
person.identifier.orcid0000-0002-0702-6700
person.identifier.orcid0000-0002-6084-6775
person.identifier.orcid0000-0003-0060-2936
person.identifier.orcid0000-0002-9197-5318
person.identifier.orcid0000-0001-9410-4772
person.identifier.orcid0000-0002-0454-9207
person.identifier.ridI-4676-2014
person.identifier.ridF-4404-2012
person.identifier.scopus-author-id36061472900
person.identifier.scopus-author-id57194785077
person.identifier.scopus-author-id14319300100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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