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t(3;7)(q27;q32) fuses BCL6 to a non-coding region at FRA7H near miR-29

Leukemia volume 22, pages 1262–1266 (2008)Cite this article

DNA breakage at chromosomal fragile sites (CFS) is believed to promote oncogenic chromosome rearrangement. Notable CFS involvement in leukemia–lymphoma (LL) includes deletions affecting WWOX (located within FRA16D), which is also fused with IGH via t(14;16)(q32;q23) in multiple myeloma, and FHIT at 3p14 (FRA3D) in B-cell lymphoma. Both lesions operate as tumor suppressors and, unlike key LL rearrangements, occur widely in solid tumors. Only 19/89 CFS have been cloned and their coordinates pinpointed.1 Recent mapping data now show that FRA8C, another leading candidate CFS in LL, lies outside the MYC breakpoint cluster at 8q24.2 Hence, there remain tantalizingly few leukemic oncogene chromosome rearrangements definitively mapped within CFS. We describe t(3;7)(q27;q32) in a B-cell lymphoma cell line, which fuses BCL6 to a conserved non-coding region within FRA7H, to serve as a unique model for neoplastic fragile site involvement in LL.

Fluorescence in situ hybridization (FISH) using bacterial artificial chromosome (BAC) and fosmid clones showed that the break at 3q27 lay within BAC RP11-211G11 and fosmid WI2802L21, which both cover the BCL6 major breakpoint region (MBR) (Figure 1b). FISH analysis placed the break at 7q32 within fosmid clone WI2452B9 (Figure 1c) amid the common fragile site FRA7H (Figure 1d) first characterized by Mishmar et al.3. Aphidicolin clastogenicity assays confirmed that RC-K8 cells are prone to breakage within FRA7H (Figure 1e). Interestingly, breakage at FRA7H favored sites in normal chromosomes against translocation derivates, implying hightened DNA stability in the latter.

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Acknowledgements

We thank Professor Batsheva Kerem and the Sanger Institute for supplying clones. This work is partially supported by the Deutsche José Carreras Leukämie-Stiftung e.V.

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  1. Department of Human and Animal Cell Cultures, DSMZ—German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

    B Schneider, S Nagel, M Kaufmann, H G Drexler & R A F MacLeod

  2. HZI—Helmholtz Center for Infection Research, Braunschweig, Germany

    S Winkelmann & J Bode

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  1. B Schneider
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  2. S Nagel
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Correspondence to R A F MacLeod.

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Schneider, B., Nagel, S., Kaufmann, M. et al. t(3;7)(q27;q32) fuses BCL6 to a non-coding region at FRA7H near miR-29. Leukemia 22, 1262–1266 (2008). https://doi.org/10.1038/sj.leu.2405025

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