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  • Original Paper
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Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma

Abstract

We recently isolated the RhoH/TTF gene by its fusion to the LAZ3/BCL6 gene, in a non-Hodgkin's lymphoma (NHL) cell line, which bore a t(3;4)(q27;p11–13) translocation. This gene encodes a novel Rho GTP-binding protein and is specifically expressed in hematopoietic tissues. We made its precise mapping at band 4p13, and described its partial genomic structure. Using fluorescence in situ hybridization and molecular analyses, we report here on the rearrangement of the RhoH/TTF gene, at band 4p13, in four cases of NHL with t(3;4)(q27;p13) translocation and its fusion to the LAZ3/BCL6 gene at band 3q27, in three of these cases. RT–PCR analysis of two cases allowed the detection of variable fusion transcripts emerging from the rearranged alleles, and in one case, a deregulated expression of both RhoH/TTF and LAZ3/BCL6 genes, by promoter substitution, was observed. We also show here another rearrangement of the RhoH/TTF gene in a patient with multiple myeloma and t(4;14)(p13;q32) translocation, with breakage within the IGH gene. It is the first report which describes the recurrent chromosomal alteration of a GTP-binding protein encoding gene, in patients with hematopoietic malignancies.

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Acknowledgements

Drs M Wetterwald, E Auxenfants, P Morel, from Dunkerque, Seclin, and Lens hospitals, are gratefully acknowledged for providing patients 3, 4, and 2 samples, respectively. We thank Dr Marie-Christine Copin for the lymph nodes material. Drs M Dyer, L Coignet, and T Rabbitts are gratefully acknowledged for giving us the IgH cosmids. The photographic work of Marie-Claire Duvieuxbourg is gratefully acknowledged. This work was supported by grants from ‘The Ligue Nationale Française contre le Cancer’, Comité du Pas de Calais, ‘The Association pour la Recherche contre le Cancer (ARC)’, Comité du Nord, the ‘Fondation contre la Leucémie’ and from the ‘Institut National de la Santé et de la Recherche Médicale’ (INSERM), France. One of us, E Dallery-Prudhomme, was recipient of a fellowship from the ‘Association pour la Recherche contre le Cancer (ARC)’.

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Preudhomme, C., Roumier, C., Hildebrand, M. et al. Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. Oncogene 19, 2023–2032 (2000). https://doi.org/10.1038/sj.onc.1203521

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