title: Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.
abstract: Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge.
  
  
  OBJECTIVE
  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.
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.|School of Biological Sciences (GEBIMOL), Pedagogical and Technological University of Colombia (UPTC), Tunja, Colombia.
authors.forename: Maribel
authors.initials: M
authors.lastname: Forero-Castro
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Robledo
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Abáigar
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.|Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: África Martín
authors.affiliation: Department of Hematology, Clinical University Hospital of Valladolid, Valladolid, Spain.
authors.forename: Maryam
authors.initials: M
authors.lastname: Arefi
authors.affiliation: Department of Pediatric Oncohematology, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Fuster
authors.affiliation: Department of Hematology, Virgen Blanca Hospital, León, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.affiliation: Department of Hematology, Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Juan N
authors.initials: JN
authors.lastname: Rodríguez
authors.affiliation: Department of Hematology, Miguel Servet Hospital, Zaragoza, Spain.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Quintero
authors.affiliation: Department of Pediatric Oncohematology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Riesco
authors.affiliation: Department of Hematology, Jerez Hospital, Jerez de la Frontera, Cádiz, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Hermosín
authors.affiliation: Department of Hematology, Río Hortega Hospital, Valladolid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: de la Fuente
authors.affiliation: Department of Hematology, Nuestra Señora de Sonsoles Hospital, Avila, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Recio
authors.affiliation: Department of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ribera
authors.affiliation: Department of Hematology, University Hospital of Burgos, Burgos, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Labrador
authors.affiliation: Department of Hematology, Rio Carrión Hospital, Palencia, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Alonso
authors.affiliation: Department of Hematology, General Hospital of Segovia, Segovia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Department of Hematology, Virgen de la Concha Hospital, Zamora, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sierra
authors.affiliation: Department of Hematology, Bierzo Hospital, León/Ponferrada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Megido
authors.affiliation: Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete-Sánchez
authors.affiliation: Cytometry Service (NUCLEUS Research Support Platform), University of Salamanca (USAL), Salamanca, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Ciudad Pizarro
authors.affiliation: Institute of Health Science Studies of Castile and León (IESCYL), Salamanca, Spain.
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: García
authors.affiliation: Department of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Salamanca, Spain.|Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Rivas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers