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Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia
Author(s) -
GarciaManero Guillermo,
Jeha Sima,
Daniel Jerry,
Williamson Jason,
Albitar Maher,
Kantarjian Hagop M.,
Issa JeanPierre J.
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11090
Subject(s) - methylation , dna methylation , epigenetics , cpg site , cancer research , medicine , microbiology and biotechnology , gene , biology , genetics , gene expression
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. Cancer 2003;97:695–702. © 2003 American Cancer Society. DOI 10.1002/cncr.11090