Repository logo
 
Publication

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer

2019Journal article Restricted
Simple item page
dc.contributor.authorLeão, Ricardo
dc.contributor.authorLee, Donghyun
dc.contributor.authorFigueiredo, Arnaldo
dc.contributor.authorHermanns, Thomas
dc.contributor.authorWild, Peter
dc.contributor.authorKomosa, Martin
dc.contributor.authorLau, Irene
dc.contributor.authorMistry, Mathew
dc.contributor.authorNunes, Nuno Miguel
dc.contributor.authorPrice, Aryeh J.
dc.contributor.authorZhang, Cindy
dc.contributor.authorLipman, Tatiana
dc.contributor.authorPoyet, Cédric
dc.contributor.authorValtcheva, Nadejda
dc.contributor.authorOehl, Kathrin
dc.contributor.authorCoelho, Hugo
dc.contributor.authorSayyid, Rashid
dc.contributor.authorGomes, Ana Melo
dc.contributor.authorPrado e Castro, Ligia
dc.contributor.authorSweet, Joan
dc.contributor.authorVinagre, João
dc.contributor.authorApolónio, Joana
dc.contributor.authorStephens, Derek
dc.contributor.authorFaleiro, Inês
dc.contributor.authorFadaak, Kamel
dc.contributor.authorRichard, Patrick O.
dc.contributor.authorKulkarni, Girish
dc.contributor.authorZlotta, Alexandre R.
dc.contributor.authorHamilton, Robert J.
dc.contributor.authorCastelo-Branco, Pedro
dc.contributor.authorTabori, Uri
dc.date.accessioned2019-07-02T13:09:23Z
dc.date.available2019-07-02T13:09:23Z
dc.date.issued2019
dc.description.abstractIn urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.pt_PT
dc.description.sponsorshipFoundation for Science and Technology, Government of Portugal SFRH/BD/102232/2014 Canadian Cancer Society Research Institute impact grant 137899pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1002/ijc.31935pt_PT
dc.identifier.issn0020-7136
dc.identifier.urihttp://hdl.handle.net/10400.1/12631
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectUrothelial bladder cancerpt_PT
dc.subjectTelomerasept_PT
dc.subjectTERT promoter methylationpt_PT
dc.subjectTERT promoter mutationspt_PT
dc.subjectRecurrencept_PT
dc.subjectProgressionpt_PT
dc.titleCombined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.endPage1684pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage1676pt_PT
oaire.citation.titleInternational Journal of Cancerpt_PT
oaire.citation.volume144pt_PT
oaire.fundingStream5876
person.familyNameApolónio
person.familyNameFaleiro
person.familyNameCastelo-Branco
person.givenNameJoana
person.givenNameInês
person.givenNamePedro
person.identifier.ciencia-id791E-9E39-2795
person.identifier.ciencia-idAD14-A2D0-3B41
person.identifier.ciencia-idE015-7F8F-5CA1
person.identifier.orcid0000-0002-9727-1813
person.identifier.orcid0000-0001-5178-3090
person.identifier.orcid0000-0002-3453-3978
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication01cf2be1-ea9f-4082-bcc6-e50fe4ad9fe1
relation.isAuthorOfPublication59bfe433-35ef-4864-8b8e-6a104202ef3c
relation.isAuthorOfPublicationbb25b5ad-1769-42be-a7d3-8fe76215aa23
relation.isAuthorOfPublication.latestForDiscoverybb25b5ad-1769-42be-a7d3-8fe76215aa23
relation.isProjectOfPublicatione13142f2-37b8-4b5a-b2cd-352e62003184
relation.isProjectOfPublication.latestForDiscoverye13142f2-37b8-4b5a-b2cd-352e62003184

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Le-o_et_al-2018-International_Journal_of_Cancer.pdf
Size:
587.15 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
3.46 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

FCB2-Artigos (em revistas ou actas indexadas)