TY - JOUR
T1 - Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia
AU - Fabris, Sonia
AU - Bollati, Valentina
AU - Agnelli, Luca
AU - Morabito, Fortunato
AU - Motta, Valeria
AU - Cutrona, Giovanna
AU - Matis, Serena
AU - Recchia, Anna Grazia
AU - Gigliotti, Vincenzo
AU - Gentile, Massimo
AU - Deliliers, Giorgio Lambertenghi
AU - Bertazzi, Pier Alberto
AU - Ferrarini, Manlio
AU - Neri, Antonino
AU - Baccarelli, Andrea
PY - 2011/2
Y1 - 2011/2
N2 - 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 seven 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.
AB - 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 seven 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.
KW - Alu
KW - Chronic lymphocytic leukemia
KW - DNA methyltransferases
KW - LINE-1
KW - SAT-α
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U2 - 10.4161/epi.6.2.13528
DO - 10.4161/epi.6.2.13528
M3 - Article
C2 - 20930513
AN - SCOPUS:79951499200
VL - 6
SP - 188
EP - 194
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 2
ER -