Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Feb 13

PMID 26872047

Citations 22

Authors

Maribel Forero-Castro

Cristina Robledo

Rocio Benito

Maria Abaigar

Ana Africa Martin

Maryam Arefi

Jose Luis Fuster

Natalia de Las Heras

Juan N Rodriguez

Jonathan Quintero

Susana Riesco

Lourdes Hermosin

Ignacio de la Fuente

Isabel Recio

Jordi Ribera

Jorge Labrador

Jose M Alonso

Carmen Olivier

Magdalena Sierra

Marta Megido

Luis A Corchete-Sanchez

Juana Ciudad Pizarro

Juan Luis Garcia

Jose M Ribera

Jesus M Hernandez-Rivas

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge.

Aims: 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.

Citing Articles

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[Multiple myeloma with chromothripsis: three cases report].

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