Journal Article

DKFZ-2017-00388

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia.

Claus, R. (First author)DKFZ* ; Lucas, D. M. ; Ruppert, A. S. ; Williams, K. E. ; Weng, D. ; Patterson, K. ; Zucknick, M.DKFZ* ; Oakes, C. C.DKFZ* ; Rassenti, L. Z. ; Greaves, A. W. ; Geyer, S. ; Wierda, W. G. ; Brown, J. R. ; Gribben, J. G. ; Barrientos, J. C. ; Rai, K. R. ; Kay, N. E. ; Kipps, T. J. ; Shields, P. ; Zhao, W. ; Grever, M. R. ; Plass, C.DKFZ* ; Byrd, J. C.

2014
HighWire Press Stanford, Calif.

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/blood-2014-02-555722

Abstract: ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (<20%) had significantly shortened time to first treatment (TT) and overall survival (OS) (P < .0001). For TT, low methylation defined a large subset of ZAP-70 protein-negative cases with significantly shortened TT (median, 8.0 vs 3.9 years for high vs low methylation; hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.25-0.74). Conversely, 16 ZAP-70 protein-positive cases with high methylation had poor outcome (median, 1.1 vs 2.3 years for high vs low methylation; HR = 1.62; 95% CI, 0.87-3.03). For OS, ZAP-70 methylation was the strongest risk factor; CD38 and ZAP-70 expression or IGHV status did not significantly improve OS prediction. A pyrosequencing assay was established that reproduced the MassARRAY data (κ coefficient > 0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL.

Keyword(s): Biomarkers, Tumor ; Immunoglobulin Variable Region ; ZAP-70 Protein-Tyrosine Kinase ; ZAP70 protein, human

---

Contributing Institute(s):

1. Epigenomik und Krebsrisikofaktoren (C010)
2. Biostatistik (C060)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2014

---

Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---