PLoS ONE (Jan 2016)

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

  • Maribel Forero-Castro,
  • Cristina Robledo,
  • Rocío Benito,
  • María Abáigar,
  • Ana África Martín,
  • Maryam Arefi,
  • José Luis Fuster,
  • Natalia de Las Heras,
  • Juan N Rodríguez,
  • Jonathan Quintero,
  • Susana Riesco,
  • Lourdes Hermosín,
  • Ignacio de la Fuente,
  • Isabel Recio,
  • Jordi Ribera,
  • Jorge Labrador,
  • José M Alonso,
  • Carmen Olivier,
  • Magdalena Sierra,
  • Marta Megido,
  • Luis A Corchete-Sánchez,
  • Juana Ciudad Pizarro,
  • Juan Luis García,
  • José M Ribera,
  • Jesús M Hernández-Rivas

DOI
https://doi.org/10.1371/journal.pone.0148972
Journal volume & issue
Vol. 11, no. 2
p. e0148972

Abstract

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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.