Global DNA hypomethylation affecting repeat sequences has been reported in different cancer types. Herein, we investigated the methylation levels of repetitive DNA elements in chronic lymphocytic leukemia (CLL), their correlation with the major cytogenetic and molecular features, and clinical relevance in predicting therapy-free survival (TFS). A quantitative bisulfite-PCR Pyrosequencing method was used to evaluate methylation of Alu, long interspersed nuclear elements-1 (LINE-1) and satellite-α (SAT-α) sequences in 77 untreated early-stage (Binet A) CLL patients. Peripheral B-cells from 7 healthy donors were used as controls. Methylation levels (median %5mC) were lower in B-CLLs compared with controls (21.4 vs. 25.9; 66.8 vs. 85.7; 84.0, vs. 88.2 for Alu, LINE-1 and SAT-α, respectively) (p < 0.001). Among CLL patients, a significant association was observed with 17p13.1 deletion (16.8 vs. 22.4; 51.2 vs. 68.5; 52.6 vs. 85.0, for Alu, LINE-1 and SAT-α) but not with other major genetic lesions, IgVH mutation status, CD38 or ZAP-70 expression. Follow-up analyses showed that lower SAT-α methylation levels appeared to be an independent prognostic marker significantly associated with shorter TFS. Our study extended previous limited evidences in methylation of repetitive sequences in CLL suggesting an important biological and clinical relevance in the disease.
Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia / S. Fabris, V. Bollati, L. Agnelli, F. Morabito, V. Motta, G. Cutrona, S. Matis, A. Grazie Recchia, V. Gigliotti, M. Gentile, G. Lambertenghi Deliliers, P.A. Bertazzi, M. Ferrarini, A. Neri, A. Baccarelli. - In: EPIGENETICS. - ISSN 1559-2294. - 6:2(2011 Feb 01), pp. 188-194.
|Titolo:||Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia|
FABRIS, SONIA (Primo)
BOLLATI, VALENTINA (Secondo)
NERI, ANTONINO (Penultimo)
BACCARELLI, ANDREA (Ultimo)
|Parole Chiave:||Alu; Chronic lymphocytic leukemia; DNA methyltransferases; LINE-1; SAT-α|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
Settore MED/15 - Malattie del Sangue
|Data di pubblicazione:||1-feb-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4161/epi.6.2.13528|
|Appare nelle tipologie:||01 - Articolo su periodico|