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| Status |
Public on Mar 01, 2010 |
| Title |
IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis-relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A, and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS), were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk patients with IKZF1 deletions exhibited a ~12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone non-high-risk-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification.
Affymetrix NspI 250k array data of 34 paired diagnosis and relapse samples of pediatric ALL. From 13 patients a complete remission sample was available. Four cases had 2 relapses.
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| Overall design |
Genomic DNA from 86 bone marrow or periphearal blood was hybridized on Affymetrix NspI SNP-based arrays according to manufacturer's procedures
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| Contributor(s) |
Kuiper RP, Waanders E, van der Velden VH, van Reijmersdal SV, Venkatachalam R, Scheijen B, Sonneveld E, van Dongen JM, Veerman AP, van Leeuwen FN, van Kessel AG, Hoogerbrugge PM |
| Citation(s) |
20445578 |
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| Submission date |
Feb 16, 2010 |
| Last update date |
May 17, 2017 |
| Contact name |
Roland P. Kuiper |
| E-mail(s) |
r.kuiper@antrg.umcn.nl, e.verwiel@antrg.umcn.nl
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| Phone |
+31243610868
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| Fax |
+31243668752
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| Organization name |
Radboud University Nijmegen Medical Centre
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| Department |
Human Genetics
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| Street address |
Geert Grooteplein 10
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| City |
Nijmegen |
| ZIP/Postal code |
6525GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL3718 |
[Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array |
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| Samples (86)
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| Relations |
| BioProject |
PRJNA125447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20353_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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