title: ZAP-70 intron1 DNA methylation status: determination by pyrosequencing in B chronic lymphocytic leukemia.
abstract: ZAP-70 expression is a strong prognostic indicator in chronic lymphocytic leukemia. However, ZAP-70 quantification 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.
authors: GRECAN, Centre François Baclesse, Université de Caen Basse-Normandie, Caen Cedex, France. chantepie-s@chu-caen.fr
authors: Sylvain P
authors: SP
authors: Chantepie
authors: Dominique
authors: D
authors: Vaur
authors: Christoph
authors: C
authors: Grunau
authors: Véronique
authors: V
authors: Salaün
authors: Mélanie
authors: M
authors: Briand
authors: Jean-Jacques
authors: JJ
authors: Parienti
authors: Natacha
authors: N
authors: Heutte
authors: Stéphane
authors: S
authors: Cheze
authors: Mikel
authors: M
authors: Roussel
authors: Pascal
authors: P
authors: Gauduchon
authors: Michel
authors: M
authors: Leporrier
authors: Sophie
authors: S
authors: Krieger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007438:Introns / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human