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Cytogenetics and Molecular Genetics

Novel FISH probes designed to detect IGK-MYC and IGL-MYC rearrangements in B-cell lineage malignancy identify a new breakpoint cluster region designated BVR2

Leukemia volume 20, pages 1790–1799 (2006)Cite this article

Abstract

Detection of translocations involving MYC at 8q24.1 in B-cell lineage malignancies (BCL) is important for diagnostic and prognostic purposes. However, routine detection of MYC translocations is often hampered by the wide variation in breakpoint location within the MYC region, particularly when a gene other than IGH, such as IGK or IGL, is involved. To address this issue, we developed and validated four fluorescence in situ hybridization (FISH) probes: two break apart probes to detect IGK and IGL translocations, and two dual-color, dual-fusion FISH (D-FISH) probes to detect IGK-MYC and IGL-MYC. MYC rearrangements (four IGK-MYC, 12 IGL-MYC and four unknown partner gene-MYC) were correctly identified in 20 of 20 archival BCL specimens known to have MYC rearrangements not involving IGH. Seven specimens, all of which lacked MYC rearrangements using a commercial IGH/MYC D-FISH probe, were found to have 8q24 breakpoints within a cluster region >350–645 kb 3′ from MYC, provisionally designated as Burkitt variant rearrangement region 2 (BVR2). FISH is a useful ancillary tool in identifying MYC rearrangements. In light of the discovery of the distally located BVR2 breakpoint cluster region, it is important to use MYC FISH probes that cover a breakpoint region at least 1.0 Mb 3′ of MYC.

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Acknowledgements

We thank Asli N Silahtaroglu, MSc, PhD, of the Wilhelm Johannsen Centre for Functional Genome Research (Copenhagen, Denmark) for kindly providing Burkitt lymphoma (BL) cell lines JI, BL2, BL60 and LY91; Bruce A Roe, PhD and Fares Najar, PhD of the University of Oklahoma (Norman, OK) for providing proprietary BAC clones used in our pilot studies; Peter J Steiner (Mayo Presentation Design Department) for providing expert help with the manuscript figures by using his superlative skill with Adobe Illustrator and Adobe Photoshop; Judy E Allen (Mayo Cytogenetics Lab) for kindly retrieving Mayo archival metaphase specimens; Jack L Spurbeck (Mayo Cytogenetics Lab) for reviewing karyotypes from the Mayo archives; and the Mayo Molecular Cytogenetics Core Facility for use of their equipment to perform much of this study. Supported in part by Grant CA97274 from the National Institutes of Health, Bethesda, MD, USA.

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  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    R R Einerson, M E Law, H E Blair, P J Kurtin, R F McClure, R P Ketterling, H C Flynn, A Dogan & E D Remstein

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Einerson, R., Law, M., Blair, H. et al. Novel FISH probes designed to detect IGK-MYC and IGL-MYC rearrangements in B-cell lineage malignancy identify a new breakpoint cluster region designated BVR2. Leukemia 20, 1790–1799 (2006). https://doi.org/10.1038/sj.leu.2404340

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