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Title: Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.
Authors: Forero-Castro, Maribel
Robledo, Cristina
Benito, Rocío
Abáigar, María
África Martín, Ana
Arefi, Maryam
Fuster, José Luis
de Las Heras, Natalia
Rodríguez, Juan N
Quintero, Jonathan
Riesco, Susana
Hermosín, Lourdes
de la Fuente, Ignacio
Recio, Isabel
Ribera, Jordi
Labrador, Jorge
Alonso, José M
Olivier, Carmen
Sierra, Magdalena
Megido, Marta
Corchete-Sánchez, Luis A
Ciudad Pizarro, Juana
García, Juan Luis
Ribera, José M
Hernández-Rivas, Jesús M
metadata.dc.subject.mesh: Adolescent
Aged, 80 and over
Biomarkers, Tumor
Child, Preschool
Comparative Genomic Hybridization
DNA Copy Number Variations
Gene Dosage
Gene Frequency
Genetic Markers
Genetic Predisposition to Disease
Genome-Wide Association Study
Infant, Newborn
Kaplan-Meier Estimate
Middle Aged
Multivariate Analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Treatment Outcome
Young Adult
Issue Date: 12-Feb-2016
Abstract: Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.
metadata.dc.identifier.doi: 10.1371/journal.pone.0148972
Appears in Collections:Producción 2020

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