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dc.contributor.authorAbáigar, María-
dc.contributor.authorRobledo, Cristina-
dc.contributor.authorBenito, Rocío-
dc.contributor.authorRamos, Fernando-
dc.contributor.authorDíez-Campelo, María-
dc.contributor.authorHermosín, Lourdes-
dc.contributor.authorSánchez-del-Real, Javier-
dc.contributor.authorAlonso, Jose M.-
dc.contributor.authorCuello, Rebeca-
dc.contributor.authorMegido, Marta-
dc.contributor.authorRodríguez, Juan-Nicolas-
dc.contributor.authorMartín-Núñez, Guillermo-
dc.contributor.authorAguilar, Carlos-
dc.contributor.authorVargas, Manuel-
dc.contributor.authorMartín, Ana-África-
dc.contributor.authorGarcía, Juan L.-
dc.contributor.authorKohlmann, Alexander-
dc.contributor.authorCañizo, María Consuelo del-
dc.contributor.authorHernández, Jesús M.-
dc.identifierdoi: 10.1371/journal.pone.0164370-
dc.identifiere-issn: 1932-6203-
dc.identifier.citationPLoS ONE 11(10): e0164370 (2016)-
dc.description.abstractTo explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases. 285 abnormalities were identified in 71 patients (23.6%). Three high-risk MDS cases (1.2%) displayed chromothripsis involving exclusively chromosome 13 and affecting some cancer genes: FLT3, BRCA2 and RB1. All three cases carried TP53 mutations as revealed by NGS. Moreover, in the whole series, the integrative analysis of aCGH and NGS enabled the identification of cryptic recurrent deletions in 2p23.3 (DNMT3A; n = 2.8%), 4q24 (TET2; n = 10%) 17p13 (TP53; n = 8.5%), 21q22 (RUNX1; n = 7%), and Xp11.4 (BCOR; n = 2.8%), while mutations in the non-deleted allele where found only in DNMT3A (n = 1), TET2 (n = 3), and TP53 (n = 4). These cryptic abnormalities were detected mainly in patients with normal (45%) or non-informative (15%) karyotype by conventional cytogenetics, except for those with TP53 deletion and mutation (15%), which had a complex karyotype. In addition to wellknown copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed thepresence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located.-
dc.description.sponsorshipThis work was partially supported by Grants from the Spanish Fondo de Investigaciones Sanitarias FIS (PI12/00281); Proyectos de Investigación del SACYL (BIO/SA47/13; BIO/SA52/14; GRS/874/A13; GRS 994/A/14); COST Action “EuGESMA”(BM0801); Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanis Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa”(Innocampus, CEI2010-1-0010) (RD12/0036/0069; RD12/0036/0029; RD12/0036/0044); and the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement n˚306242-NGS-PTL. MA was supported by a “Junta para Ampliación de Estudios”fellowship [09-02402] of the Spanish National Research Council (Consejo Superior de Investigaciones Científicas, CSIC), cofunded by the European Social Fund, and by a “Grant from Fundación Española de Hematología y Hemoterapia”. AK is employed by AstraZeneca-
dc.publisherPublic Library of Science-
dc.relation.isversionofPublisher's version-
dc.titleChromothripsis is a recurrent genomic abnormality in high-risk myelodysplastic syndromes-
dc.description.versionPeer Reviewed-
dc.contributor.funderSociedad Española de Hematología y Hemoterapia-
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España)-
dc.contributor.funderEuropean Commission-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
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