Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis.

Pavlovic, Milica, 1985-; Arnal-Estapé, Anna; Rojo, Federico; Bellmunt, Anna; Tarragona, Maria; Guiu, Marc; Planet, Evarist; Garcia-Albéniz, Xabier; Morales, Mònica; Urosevic, Jelena; Gawrzak, Sylwia; Rovira Guerín, Ana; Prat, Aleix; Nonell Mazelon, Lara, 1972-; Lluch, Ana; Jean-Mairet, Joël; Coleman, Robert; Albanell Mestres, Joan; Gomis, Roger R.

Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis.

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dc.contributor.author Pavlovic, Milica, 1985-ca
dc.contributor.author Arnal-Estapé, Anna ca
dc.contributor.author Rojo, Federicoca
dc.contributor.author Bellmunt, Anna ca
dc.contributor.author Tarragona, Maria ca
dc.contributor.author Guiu, Marcca
dc.contributor.author Planet, Evaristca
dc.contributor.author Garcia-Albéniz, Xabierca
dc.contributor.author Morales, Mònicaca
dc.contributor.author Urosevic, Jelena ca
dc.contributor.author Gawrzak, Sylwia ca
dc.contributor.author Rovira Guerín, Anaca
dc.contributor.author Prat, Aleixca
dc.contributor.author Nonell Mazelon, Lara, 1972-ca
dc.contributor.author Lluch, Anaca
dc.contributor.author Jean-Mairet, Joël ca
dc.contributor.author Coleman, Robert ca
dc.contributor.author Albanell Mestres, Joanca
dc.contributor.author Gomis, Roger R.ca
dc.date.accessioned 2016-02-02T12:30:24Z
dc.date.available 2016-02-02T12:30:24Z
dc.date.issued 2015
dc.description.abstract BACKGROUND: There are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification of mediators of bone metastasis could be of clinical interest. METHODS: A de novo unbiased screening approach based on selection of highly bone metastatic breast cancer cells in vivo was used to determine copy number aberrations (CNAs) associated with bone metastasis. The CNAs associated with bone metastasis were examined in independent primary breast cancer datasets with annotated clinical follow-up. The MAF gene encoded within the CNA associated with bone metastasis was subjected to gain and loss of function validation in breast cancer cells (MCF7, T47D, ZR-75, and 4T1), its downstream mechanism validated, and tested in clinical samples. A multivariable Cox cause-specific hazard model with competing events (death) was used to test the association between 16q23 or MAF and bone metastasis. All statistical tests were two-sided. RESULTS: 16q23 gain CNA encoding the transcription factor MAF mediates breast cancer bone metastasis through the control of PTHrP. 16q23 gain (hazard ratio (HR) for bone metastasis = 14.5, 95% confidence interval (CI) = 6.4 to 32.9, P < .001) as well as MAF overexpression (HR for bone metastasis = 2.5, 95% CI = 1.7 to 3.8, P < .001) in primary breast tumors were specifically associated with risk of metastasis to bone but not to other organs. CONCLUSIONS: These results suggest that MAF is a mediator of breast cancer bone metastasis. 16q23 gain or MAF protein overexpression in tumors may help to select patients at risk of bone relapse.ca
dc.description.sponsorship MP and SG is supported by “La Caixa” PhD fellowship program. AAE and AB hold PhD fellowships from the Spanish Ministerio de Ciencia e Innovación (MICINN). MTS is supported by the IRB Barcelona PhD program. JU is a “Juan de la Cierva” Researcher (MICINN). FIS PI12/00680, PI12/01552, and PI12/01421 supported JA, ALl, and FR, respectively. JA, ALl, and AP were part of RD12/0036/0051, RD12/0036/0070, and RD12/0036/0042, and FR is part of biobanc RD/09/0076/00101. JA and FR are recipients of intensification grant ISCIII, 2009SGR321, XBTC, MARBiobanc, and Cellex. RRG was supported by the Institució Catalana de Recerca i Estudis Avançats. Support and structural funds were provided by the BBVA Foundation, the Generalitat de Catalunya (2014 SGR 535), and the Spanish Ministerio de Ciencia e Innovación (MICINN) (SAF2013-46196) to RRG.
dc.format.mimetype application/pdfca
dc.identifier.citation Pavlovic M, Arnal-Estapé A, Rojo F, Bellmunt A, Tarragona M, Guiu M. et al. Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis. J Natl Cancer Inst. 2015 Sep 15;107(12):djv256. DOI: 10.1093/jnci/djv256.ca
dc.identifier.doi http://dx.doi.org/10.1093/jnci/djv256
dc.identifier.issn 0027-8874
dc.identifier.uri http://hdl.handle.net/10230/25715
dc.language.iso engca
dc.publisher Oxford Open ca
dc.relation.ispartof Journal of the National Cancer Institute. 2015 Sep 15;107(12):djv256
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-46196
dc.rights © Roger R. Gomis 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.comca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ca
dc.subject.other Mama -- Càncer -- Aspectes genèticsca
dc.subject.other Ossos -- Càncerca
dc.title Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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