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Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia

Authors

  • Annet Simons,

    Corresponding author
    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
    • Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands
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  • Marian Stevens-Kroef,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Najat El Idrissi-Zaynoun,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Sabine van Gessel,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Daniel Olde Weghuis,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Eva van den Berg,

    1. Department of Medical Genetics, University Medical Centre Groningen, Groningen, The Netherlands
    2. Dutch Childhood Oncology Group, The Hague, The Netherlands
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  • Esmé Waanders,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Peter Hoogerbrugge,

    1. Dutch Childhood Oncology Group, The Hague, The Netherlands
    2. Department of Pediatric Hemato-Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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  • Roland Kuiper,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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  • Ad Geurts van Kessel

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands
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Abstract

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.

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