Copy number alterations in childhood acute lymphoblastic leukemia and their association with minimal residual disease

被引:17
作者
Steinemann, Doris [1 ]
Cario, Gunnar [2 ]
Stanulla, Martin
KarawajeW, Leonid
Tauscher, Marcel [1 ]
Weigmann, Anja [1 ]
Ghring, Gudrun [1 ]
Ludwig, Wolf-Dieter [3 ]
Harbott, Jochen [4 ]
Radiwimmer, Bernhard [5 ]
Bartram, Claus [6 ]
Lichter, Peter [5 ]
Schrappe, Martin [2 ]
Schlegelberger, Brigitte [1 ]
机构
[1] Hannover Med Sch, Inst Cell & Mol Pathol, D-30625 Hannover, Germany
[2] Univ Hosp Schleswig Holstein, Dept Pediat, Campus Kiel, Germany
[3] Charite, Robert Rossle Klin, HELIOS Klinikum Berlin, Campus Berlin Buch, Germany
[4] Univ Giessen, Giessen, Germany
[5] Deutsch Krebsforschungszentrum, Dept Mol Genet, D-6900 Heidelberg, Germany
[6] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany
关键词
D O I
10.1002/gcc.20557
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In vivo response to initial therapy, as assessed by determination of minimal residual disease (MRD) after 5 and 12 weeks of treatment, has evolved as a strong prognostic factor in children with acute lymphoblastic leukemia (ALL) treated according to the BFM regime. Individual treatment response may be influenced by copy number alterations (CNA) leading to altered gene expression. We aimed to evaluate CNA using high-resolution array-comparative genomic hybridization (array-CGH) in different treatment-response groups. Leukemic genomic profiles of 25 standard risk (MRD-SR) and 25 high risk (MRD-HR) patients were compared. CNAs were found in 46/50 patients (92%). The most significant difference was a gain of 1q23-qter because of an unbalanced t(1; 19), found in 10/25 MRD-SR patients, but in none of the MRD-HR patients (P < 0.001). The most frequent Cl in the MRD-HR group were deletions of genomic regions harboring the immunoglobulin genes (1g), e.g., 2p11.2 in 60% of MRD-HR compared to 28% of MRD-SR (P = 0.045). Combining all 1g loci, significantly more MRD-HR than MRD-SR patients displayed deletions (17:8 patients, P = 0.02). Frequency of other CNAs, such as loss of 9p21 or gains of 21q, did not differ strongly between the two patient groups. This is the first study evaluating the clinical significance of CNA as detected by array-CGH in childhood ALL and the first to suggest that such analyses may provide clinically important data. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:471 / 480
页数:10
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