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Cryptic chromosomal aberrations waiting to be discovered

Leukemia volume 20, pages 210–211 (2006)Cite this article

Leukemias are frequently characterized by the presence of chromosomal rearrangements, but 40–50% of these malignancies present with a normal karyotype, as determined by standard cytogenetic analysis. We now know that a significant fraction of the patients with normal karyotype, do harbor chromosomal rearrangements that escape detection by routine cytogenetics, as again highlighted by the study of Paulsson et al.1 in this issue of Leukemia. Well known examples include the t(12;21)(p13;q22)/ETV6-RUNX1 fusion in B-cell acute lymphoblastic leukemia (B-ALL),2 the t(5;14)(q35;q32)/TLX3 overexpression, and the recently discovered episomes (small extrachromosomal elements) carrying the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia (T-ALL),3 and the del(4)(q12q12)/FIP1L1-PDGFRA fusion in chronic eosinophilic leukemia (CEL).4 Sophisticated methods, such as microarray-comparative genomic hybridization (array-CGH) and single nucleotide polymorphism (SNP)-arrays are expected to uncover more cryptic aberrations in leukemia, including cryptic deletions and amplifications, as well as uniparental disomy, as nicely demonstrated by pioneering work by Brian Young et al.5, 6, 7 However, despite the high resolution of the current CGH- and SNP-arrays, these methods are unable to detect balanced chromosomal translocations that are not associated with DNA losses or gains. Fluorescence in situ hybridization (FISH) with gene-specific probes or multicolor FISH (M-FISH)8 is required to detect cryptic balanced chromosomal aberrations. Using M-FISH, Speleman and co-workers recently identified novel aberrations in ALL, also leading to the identification of a recurrent cryptic inv(7)(p15q34) in T-ALL,9, 10 and a specific FISH screen looking for ABL1 rearrangements in T-ALL revealed a novel cryptic t(9;14)(q34;q32).11 In this issue of Leukemia, M-FISH revealed the presence of a novel cryptic translocation t(7;21)(p22;q22), involving the well known RUNX1 oncogene, and USP42, a gene encoding a ubiquitin specific protease, a family of proteins not previously implicated in the pathogenesis of leukemia.1

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Acknowledgements

Jan Cools is a postdoctoral researcher of the FWO-Vlaanderen. Supported by the FWO-Vlaanderen, the Belgian Federation against Cancer, and the European Hematology Association.

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  1. Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium

    I Lahortiga & J Cools

  2. Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain

    I Lahortiga

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Correspondence to J Cools.

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Lahortiga, I., Cools, J. Cryptic chromosomal aberrations waiting to be discovered. Leukemia 20, 210–211 (2006). https://doi.org/10.1038/sj.leu.2404078

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