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Title: Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes.
Authors: Abáigar, María
Robledo, Cristina
Benito, Rocío
Ramos, Fernando
Díez-Campelo, María
Hermosín, Lourdes
Sánchez-Del-Real, Javier
Alonso, Jose M
Cuello, Rebeca
Megido, Marta
Rodríguez, Juan N
Martín-Núñez, Guillermo
Aguilar, Carlos
Vargas, Manuel
Martín, Ana A
García, Juan L
Kohlmann, Alexander
Del Cañizo, M Consuelo
Hernández-Rivas, Jesús M
metadata.dc.subject.mesh: Adolescent
Aged, 80 and over
Chromosome Aberrations
Chromosomes, Human, Pair 13
Comparative Genomic Hybridization
Core Binding Factor Alpha 2 Subunit
DNA (Cytosine-5-)-Methyltransferases
DNA Copy Number Variations
DNA Methyltransferase 3A
DNA Mutational Analysis
DNA-Binding Proteins
High-Throughput Nucleotide Sequencing
Middle Aged
Myelodysplastic Syndromes
Proto-Oncogene Proteins
Tumor Suppressor Protein p53
Young Adult
Issue Date: 14-Oct-2016
Abstract: To 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 well-known copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed the presence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located.
metadata.dc.identifier.doi: 10.1371/journal.pone.0164370
Appears in Collections:Producción 2020

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