ZAP-70 intron1 DNA methylation status: Determination by pyrosequencing in B chronic lymphocytic leukemia

被引:19
作者
Chantepie, Sylvain P. [1 ,2 ,3 ]
Vaur, Dominique [2 ,3 ]
Grunau, Christoph [4 ]
Salauen, Veronique [5 ]
Briand, Melanie [2 ]
Parienti, Jean-Jacques [6 ]
Heutte, Natacha [2 ]
Cheze, Stephane
Roussel, Mikel [7 ]
Gauduchon, Pascal [2 ]
Leporrier, Michel
Krieger, Sophie [2 ,3 ]
机构
[1] Univ Caen Basse Normandie, Hematol Serv, CHU Caen, Hematol Clin, F-14033 Caen, France
[2] Univ Caen Basse Normandie, Ctr Francois Baclesse, GRECAN, F-14033 Caen, France
[3] Univ Caen Basse Normandie, Ctr Francois Baclesse, Lab Biol Clin & Oncol, F-14033 Caen, France
[4] CNRS, UMR 5244, Pergpignan, France
[5] CHU Caen, Hematol Lab, F-14000 Caen, France
[6] CHU Caen, Serv Rech Clin & Biostat, F-14000 Caen, France
[7] CHU Pontchaillou Rennes, Hematol Lab, Rennes, France
关键词
ZAP-70; CLL; DNA methylation; Pyrosequencing; Epigenetics; VARIABLE-REGION MUTATIONS; EXPRESSION; DISEASE; CD38; PHENOTYPE; SURVIVAL; REVEALS; CANCER; GENES; CELLS;
D O I
10.1016/j.leukres.2009.10.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ZAP-70 expression is a strong prognostic indicator in chronic lymphocytic leukemia. However, ZAP-70 quanti. cation by flow cytometry lacks sufficient standardization. Based upon the correlation between ZAP-70 expression and its gene methylation status, we have developed a quantitative pyrosequencing assay for the determination of ZAP-70 methylation adapted for routine use. Methylation in four CpG pairs (C-223, C-243, C-254, and C-267) in the first intron of ZAP-70 is associated with repression of ZAP-70. Moreover, it correlates with CD38 expression (n = 111, p<.0001), IgHv mutation status (n = 106, p<.0001), time to treatment (p<.0001), and overall survival (p=.0014). Pyrosequencing of ZAP-70 provides a good alternative to flow cytometry. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:800 / 808
页数:9
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