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Lymphoma

Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma

Leukemia volume 14, pages 1967–1974 (2000)Cite this article

Abstract

The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other groups. RT-PCR analysis and DNA sequencing demonstrated the expression of an API2-MALT1 fusion transcript in 18/24 gastral and extragastral MALT-type lymphomas. In none of 10 LBLs was a translocation specific RT-PCR product detected. Five variants of the fusion transcript were identified and in all instances the open reading frame of the fused portion of the MALT1 gene was maintained. The molecular analysis of these variants allowed the design of optimised assays for the diagnosis of the API2-MALT1 gene rearrangement.

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Acknowledgements

The human PAC library was created at Roswell Park Cancer Institute by Panos A Ioannou (RPCI-1), Chira Chen and Baohui Zhao (RPCI-3), and Baohui Zhao (RPCI-4 and 5). High density filters and clones were kindly provided by the Resource Center/Primary Database of the German Human Genome Project, Berlin, Germany. Michael James kindly provided information on the physical map of the YACs. The authors gratefully thank Simone Schindelmann, Sandra Weitz and Ralf Klären for their technical assistance. Finally, we also acknowledge Peter Marynen for open discussion. This work was supported by grants from the Deutsche Forschungsgemeinschaft (Ka 1449/1–1) and the Sander-Stiftung (94.025.2 and 98.086.1)

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Authors and Affiliations

  1. ‘Organisation komplexer Genome’, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    J Kalla, C Schaffner, S Wolf & P Lichter

  2. Innere Medizin III, Universität Ulm, Ulm, Germany

    S Stilgenbauer & H Döhner

  3. Pathologisches Institut der Universität Würzburg, Würzburg, Germany

    G Ott, A Greiner, A Rosenwald & HK Müller-Hermelink

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Kalla, J., Stilgenbauer, S., Schaffner, C. et al. Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma. Leukemia 14, 1967–1974 (2000). https://doi.org/10.1038/sj.leu.2401918

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