ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorBueno, R. C.
dc.creatorCanevari, R. A.
dc.creatorVillacis, R. A. R.
dc.creatorDomingues, Maria Aparecida Custódio
dc.creatorCaldeira, J. R. F.
dc.creatorRocha, R. M.
dc.creatorLinde, Sandra Aparecida Drigo
dc.creatorRogatto, Silvia Regina
dc.date2014-12-03T13:10:37Z
dc.date2016-10-25T20:10:55Z
dc.date2014-12-03T13:10:37Z
dc.date2016-10-25T20:10:55Z
dc.date2014-01-01
dc.date.accessioned2017-04-06T06:21:21Z
dc.date.available2017-04-06T06:21:21Z
dc.identifierAnnals Of Oncology. Oxford: Oxford Univ Press, v. 25, n. 1, p. 69-75, 2014.
dc.identifier0923-7534
dc.identifierhttp://hdl.handle.net/11449/112323
dc.identifierhttp://acervodigital.unesp.br/handle/11449/112323
dc.identifier10.1093/annonc/mdt421
dc.identifierWOS:000331268800010
dc.identifierhttp://dx.doi.org/10.1093/annonc/mdt421
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/923088
dc.descriptionBackground: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear.Patients and methods: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic hybridization (aCGH) in 42 tumours.Results: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P < 0.001), reduced disease-free survival (DFS, P < 0.001) and cancer-specific survival (CSS, P < 0.001). Multivariate analysis indicated ATM protein expression as an independent prognostic marker for DFS (P = 0.001, HR = 0.579) and CSS (P = 0.001, HR = 0.554). ATM copy number loss was detected in 12% of tumours and associated with lower mRNA levels. miR-421 over-expression was detected in 36.5% of cases which exhibit lower ATM transcript levels (P = 0.075, r = -0.249).Conclusions: The data suggest that ATM protein expression is an independent prognostic marker in sporadic BC. Gene copy number loss and miR-421 over-expression may be involved in ATM deregulation in BC.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherOxford University Press
dc.relationAnnals of Oncology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectataxia-telangiectasia-mutated (ATM) gene
dc.subjectbreast cancer
dc.subjectcopy number alteration
dc.subjectmicroRNA
dc.subjectprognostic marker
dc.titleATM down-regulation is associated with poor prognosis in sporadic breast carcinomas
dc.typeOtro


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