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Variants on the pro...
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Heikkinen, Tuomas
(författare)
Variants on the promoter region of PTEN affect breast cancer progression and patient survival
- Artikel/kapitelEngelska2011
Förlag, utgivningsår, omfång ...
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2011-12-15
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Springer Science and Business Media LLC,2011
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-171137
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171137URI
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https://doi.org/10.1186/bcr3076DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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INTRODUTION:The PTEN gene, a regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway, is mutated in various cancers and its expression has been associated with tumor progression in a dose-dependent fashion. We investigated the effect of germline variation in the promoter region of the PTEN gene on clinical characteristics and survival in breast cancer.METHODS:We screened the promoter region of the PTEN gene for germline variation in 330 familial breast cancer cases and further determined the genotypes of three detected PTEN promoter polymorphisms -903GA, -975GC, and -1026CA in a total of 2,412 breast cancer patients to evaluate the effects of the variants on tumor characteristics and disease outcome. We compared the gene expression profiles in breast cancers of 10 variant carriers and 10 matched non-carriers and performed further survival analyses based on the differentially expressed genes.RESULTS: All three promoter variants associated with worse prognosis. The Cox's regression hazard ratio for 10-year breast cancer specific survival in multivariate analysis was 2.01 (95% CI 1.17 to 3.46) P = 0.0119, and for 5-year breast cancer death or distant metastasis free survival 1.79 (95% CI 1.03 to 3.11) P = 0.0381 for the variant carriers, indicating PTEN promoter variants as an independent prognostic factor. The breast tumors from the promoter variant carriers exhibited a similar gene expression signature of 160 differentially expressed genes compared to matched non-carrier tumors. The signature further stratified patients into two groups with different recurrence free survival in independent breast cancer gene expression data sets.CONCLUSIONS:Inherited variation in the PTEN promoter region affects the tumor progression and gene expression profile in breast cancer. Further studies are warranted to establish PTEN promoter variants as clinical markers for prognosis in breast cancer.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Greco, Dario
(författare)
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Pelttari, Liisa M
(författare)
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Tommiska, Johanna
(författare)
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Vahteristo, Pia
(författare)
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Heikkilä, Päivi
(författare)
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Blomqvist, CarlDepartment of Oncology, Helsinki University Central Hospital, Helsinki, Finland(Swepub:uu)carlblom
(författare)
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Aittomäki, Kristiina
(författare)
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Nevanlinna, Heli
(författare)
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Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Breast Cancer Research: Springer Science and Business Media LLC13:6, s. R130-1465-54111465-542X
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