Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia
Version of Record online: 31 AUG 2011
Copyright © 2011 Wiley Periodicals, Inc.
Genes, Chromosomes and Cancer
Volume 50, Issue 12, pages 969–981, December 2011
How to Cite
Simons, A., Stevens-Kroef, M., Idrissi-Zaynoun, N. E., van Gessel, S., Weghuis, D. O., van den Berg, E., Waanders, E., Hoogerbrugge, P., Kuiper, R. and van Kessel, A. G. (2011), Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia. Genes Chromosom. Cancer, 50: 969–981. doi: 10.1002/gcc.20919
- Issue online: 10 OCT 2011
- Version of Record online: 31 AUG 2011
- Manuscript Accepted: 14 JUL 2011
- Manuscript Received: 5 APR 2011
In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray-based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray-deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (<5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray-based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray-based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting. © 2011 Wiley Periodicals, Inc.