title: Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia.
abstract: BACKGROUND
  Aberrant methylation of promoter-associated cystosine-guanine (CpG) islands is an epigenetic modification of DNA frequently observed in adult patients with acute lymphocytic leukemia (ALL). This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL.
  
  
  METHODS
  To investigate the methylation characteristics of pediatric patients with ALL and to determine whether DNA methylation can explain prognostic or biologic differences between pediatric and adult patients, the authors analyzed the methylation status of 7 promoter-associated CpG islands in 16 pediatric patients with ALL and compared them with the methylation characteristics of a cohort of adult patients with ALL. The genes analyzed included the estrogen receptor gene (ER), multidrug resistance gene 1 (MDR1), p15, C-ABL, CD10, p16, and p73.
  
  
  RESULTS
  The mean methylation densities of ER, MDR1, CD10, p15, and C-ABL were 25.4%, 16.4%, 5.23%, 4.24%, and 4%, respectively. P16 was methylated in 11.7% of patients, and p73 was methylated in 17.6% of patients. One patient (6.2%) had methylation of 0 genes, 15 patients (93.7%) had methylation of >/= 1 gene, and 4 patients (25%) had methylation of 3-4 genes. Methylation of all these genes was < 2% (or methylation specific polymerase chain reaction negative) in nonneoplastic tissues. A significant inverse correlation was observed between methylation of CD10 and CD10 expression. No differences were observed between the methylation characteristics of pediatric patients and adult patients.
  
  
  CONCLUSIONS
  The results indicate that DNA methylation is common in pediatric patients with ALL and that methylation of the genes studied does not account for prognostic differences between pediatric patients and adult patients with ALL.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ggarciam@mdanderson.org
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Jerry
authors.initials: J
authors.lastname: Daniel
authors.forename: Jason
authors.initials: J
authors.lastname: Williamson
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jean-Pierre J
authors.initials: JP
authors.lastname: Issa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis