dc.contributor.author | Calvete, Oriol | |
dc.contributor.author | Martinez, Paula | |
dc.contributor.author | García Pavía, Pablo | |
dc.contributor.author | Benitez-Buelga, Carlos | |
dc.contributor.author | Paumard Hernández, Beatriz | |
dc.contributor.author | Fernandez, Victoria | |
dc.contributor.author | Dominguez, Fernando | |
dc.contributor.author | Salas, Clara | |
dc.contributor.author | Romero-Laorden, Nuria | |
dc.contributor.author | Garcia-Donas, Jesus | |
dc.contributor.author | Carrillo, Jaime | |
dc.contributor.author | Perona, Rosario | |
dc.contributor.author | Trivinõ, Juan Carlos | |
dc.contributor.author | Andrés, Raquel | |
dc.contributor.author | Cano, Juana Mariá | |
dc.contributor.author | Rivera, Bárbara | |
dc.contributor.author | Alonso-Pulpón, Luis A. | |
dc.contributor.author | Setien, Fernando | |
dc.contributor.author | Esteller, Manel | |
dc.contributor.author | Rodriguez-Perales, Sandra | |
dc.contributor.author | Bougeard, Gaelle | |
dc.contributor.author | Frebourg, Tierry | |
dc.contributor.author | Urioste, Miguel | |
dc.contributor.author | Blasco, Maria A. | |
dc.contributor.author | Benítez, Javier | |
dc.contributor.other | UAM. Departamento de Medicina | es_ES |
dc.date.accessioned | 2016-07-26T15:27:11Z | |
dc.date.available | 2016-07-26T15:27:11Z | |
dc.date.issued | 2015-09-25 | |
dc.identifier.citation | Nature Communications 6 (2015): Article 8383 | en_US |
dc.identifier.issn | 2041-1723 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/672233 | |
dc.description.abstract | Cardiac 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 | en_US |
dc.description.sponsorship | We are grateful to T. de Lange (The Rockefeller University) and K. Collins
(The University of California) for providing POT1 and TPP1 plasmids, respectively. J.B.’s
laboratory is partially funded by the Spanish Ministry of Health PI12/00070, the Spanish
Ministry of Science and Innovation (INNPRONTA 2012) and the Spanish Research
Network on Rare diseases (CIBERER). O.C. is granted by the CIBERER and C.B.-B. by
the PI12/00070 supported by FEDER funds. P.G.-P. is partially supported by the Spanish
Ministry of Health PI11/0699, PI12/01941 and RD12/0042/0066. M.A.B.’s laboratory is
funded with the Spanish Ministry of Science and Innovation, projects SAF2008-05384
and 2007-A-200950 (TELOMARKER), European Research Council Advanced grant
GA#232854, the Körber Foundation, Fundación Botín and Fundación Lilly. R.P.’ lab is
partially funded by PI11/0949 Supported by FEDER funds | en_US |
dc.format.extent | 12 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.language.iso | fra | en |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.ispartof | Nature Communications | en_US |
dc.rights | © 2015 Macmillan Publishers Limited | en_US |
dc.subject.other | Cardiac angiosarcoma | en_US |
dc.subject.other | Mutation in a breast | en_US |
dc.subject.other | Telomeres | en_US |
dc.title | A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1038/ncomms9383 | es_ES |
dc.identifier.doi | 10.1038/ncomms9383 | es_ES |
dc.identifier.publicationfirstpage | Article 8383 | es_ES |
dc.identifier.publicationlastpage | Article 8383 | es_ES |
dc.identifier.publicationvolume | 6 | es_ES |
dc.relation.projectID | Gobierno de España. PI12/00070 | es_ES |
dc.relation.projectID | Gobierno de España. PI11/0699 | es_ES |
dc.relation.projectID | Gobierno de España. PI12/01941 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2008-05384 | es_ES |
dc.relation.projectID | Gobierno de España. 2007-A-200950 TELOMARKER | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/232854 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Alonso-Pulpón Rivera, Luis Antonio (259485) | |
dc.facultadUAM | Facultad de Medicina | |