000032203 001__ 32203
000032203 005__ 20210121082901.0
000032203 0247_ $$2doi$$a10.1038/ncomms9383
000032203 0248_ $$2sideral$$a92237
000032203 037__ $$aART-2015-92237
000032203 041__ $$aeng
000032203 100__ $$aCalvete, O.
000032203 245__ $$aA mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families
000032203 260__ $$c2015
000032203 5060_ $$aAccess copy available to the general public$$fUnrestricted
000032203 5203_ $$aCardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li-Fraumeni-like (LFL) family including CAS cases, that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS. The same gene alteration is found in two other LFL families with CAS, supporting the causal effect of the identified mutation. We extend the analysis to TP53-negative LFL families with no CAS and find the same mutation in a breast AS family. The mutation is recently found once in 121, 324 studied alleles in ExAC server but it is not described in any other database or found in 1, 520 Spanish controls. In silico structural analysis suggests how the mutation disrupts POT1 structure. Functional and in vitro studies demonstrate that carriers of the mutation show reduced telomere-bound POT1 levels, abnormally long telomeres and increased telomere fragility.
000032203 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/SAF2008-05384$$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0066$$9info:eu-repo/grantAgreement/ES/ISCIII/PI12-01941$$9info:eu-repo/grantAgreement/ES/ISCIII/PI12-00070$$9info:eu-repo/grantAgreement/ES/ISCIII/PI11-0949$$9info:eu-repo/grantAgreement/ES/ISCIII/PI11-0699$$9info:eu-repo/grantAgreement/EC/FP7/232854/EU/FROM TELOMERE CHROMATIN TO STEM CELL BIOLOGY/TEL STEM CEL$$9info:eu-repo/grantAgreement/EC/FP7/200950/EU/Identification and characterization of novel human telomere-related biomarkers that aid cancer management by improving patient diagnosis, treatment selection, response monitoring, and drug development/TELOMARKER
000032203 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000032203 590__ $$a11.329$$b2015
000032203 591__ $$aMULTIDISCIPLINARY SCIENCES$$b3 / 62 = 0.048$$c2015$$dQ1$$eT1
000032203 592__ $$a6.287$$b2015
000032203 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000032203 593__ $$aPhysics and Astronomy (miscellaneous)$$c2015$$dQ1
000032203 593__ $$aChemistry (miscellaneous)$$c2015$$dQ1
000032203 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000032203 700__ $$aMartinez, P.
000032203 700__ $$aGarcia-Pavia, P.
000032203 700__ $$aBenitez-Buelga, C.
000032203 700__ $$aPaumard-Hernández, B.
000032203 700__ $$aFernandez, V.
000032203 700__ $$aDominguez, F.
000032203 700__ $$aSalas, C.
000032203 700__ $$aRomero-Laorden, N.
000032203 700__ $$aGarcia-Donas, J.
000032203 700__ $$aCarrillo, J.
000032203 700__ $$aPerona, R.
000032203 700__ $$aTrivinõ, J.C.
000032203 700__ $$0(orcid)0000-0003-0123-4274$$aAndrés, R.$$uUniversidad de Zaragoza
000032203 700__ $$aCano, J.M.
000032203 700__ $$aRivera, B.
000032203 700__ $$aAlonso-Pulpon, L.
000032203 700__ $$aSetien, F.
000032203 700__ $$aEsteller, M.
000032203 700__ $$aRodriguez-Perales, S.
000032203 700__ $$aBougeard, G.
000032203 700__ $$aFrebourg, T.
000032203 700__ $$aUrioste, M.
000032203 700__ $$aBlasco, M.A.
000032203 700__ $$aBenítez, J.
000032203 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000032203 773__ $$g6 (2015), 8383 [12 pp.]$$pNATURE COMMUNICATIONS$$tNature Communications$$x2041-1723
000032203 8564_ $$s1949696$$uhttps://zaguan.unizar.es/record/32203/files/texto_completo.pdf$$yVersión publicada
000032203 8564_ $$s93034$$uhttps://zaguan.unizar.es/record/32203/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000032203 909CO $$ooai:zaguan.unizar.es:32203$$particulos$$pdriver
000032203 951__ $$a2021-01-21-08:15:51
000032203 980__ $$aARTICLE