RT Journal Article
T1 Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.
A1 Forero-Castro, Maribel
A1 Robledo, Cristina
A1 Benito, Rocío
A1 Abáigar, María
A1 África Martín, Ana
A1 Arefi, Maryam
A1 Fuster, José Luis
A1 de Las Heras, Natalia
A1 Rodríguez, Juan N
A1 Quintero, Jonathan
A1 Riesco, Susana
A1 Hermosín, Lourdes
A1 de la Fuente, Ignacio
A1 Recio, Isabel
A1 Ribera, Jordi
A1 Labrador, Jorge
A1 Alonso, José M
A1 Olivier, Carmen
A1 Sierra, Magdalena
A1 Megido, Marta
A1 Corchete-Sánchez, Luis A
A1 Ciudad Pizarro, Juana
A1 García, Juan Luis
A1 Ribera, José M
A1 Hernández-Rivas, Jesús M
AB 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.
YR 2016
FD 2016-02-12
LK http://hdl.handle.net/10668/9829
UL http://hdl.handle.net/10668/9829
LA en
DS RISalud
RD Apr 11, 2025