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Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the α2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma

Oncogene volume 18, pages 2852–2859 (1999)Cite this article

Abstract

A region of 150 kb has been analysed around a previously isolated, lymphoma associated, translocation breakpoint located at chromosome band 11q23. This balanced and reciprocal translocation, t(11;14)(q32;q23), has been shown to result in the fusion between chromosome 11 specific sequence and the switch γ4 region of the IGH locus. The LPC gene, encoding a novel proprotein convertase belonging to the furin family, has been identified in this region. In order to characterize further the region surrounding the translocation, we have determined the detailed structure of LPC. Here we show that LPC consists of at least 16 exons covering 25 kb, and that there is a partial duplication, involving mobile genetic elements and containing LPC exons 13 – 17 in a tail – tail configuration at 65 kb downstream. Since the chromosomal breakpoint lay between these two structures, the intervening region was further analysed and shown to contain at least two unrelated genes. The previously known SM22 gene was localized close to the 3′ tail of LPC. Furthermore, we identified the gene encoding the α2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) at the chromosomal breakpoint. The position of another previously identified breakpoint was also located to within the first intron of this gene. Altogether, our results give evidence of a genomic instability of this area of 11q23 and show that Pafah1a2 and not LPC is the gene disrupted by the translocation, suggesting that deregulated Pafah1a2 may have a role in lymphomagenesis.

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Acknowledgements

This work is dedicated to Alain Lecointe, Botanist (1943 – 1998). We thank Christine Courtes and Emmanuel Douzery for assistance in the sequencing, and Debra Lillington and Michael Neat for the FISH analysis. We are grateful to Armelle Degeorges, Emmanuel Douzery and Ian Robbins for helpful discussions. NL was supported by a fellowship from the Association de la Recherche contre le Cancer. AH was supported by a grant from the Commission of European Communities, contract number F14P-CT-95-008. This work was supported in part by the Concerted Action, contract number CA-11.

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  1. Department of Medical Oncology, ICRF, Saint Bartholomew's Hospital Medical College, Charterhouse Square, London, EC1M 6BQ, UK

    Nathalie Lecointe, Joanne Meerabux, Mitsuru Ebihara, Alexander Hill & Bryan D Young

  2. I.G.M.M. — UMR CNRS 5535, 1919 route de Mende, Montpellier Cedex, 34293, France

    Nathalie Lecointe

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Lecointe, N., Meerabux, J., Ebihara, M. et al. Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the α2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma. Oncogene 18, 2852–2859 (1999). https://doi.org/10.1038/sj.onc.1202645

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