RESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 4 , Proteínas de Unión al GTP/genética , Reordenamiento Génico , Linfoma no Hodgkin/genética , Mieloma Múltiple/genética , Secuencia de Bases , Northern Blotting , Cromosomas Humanos Par 3 , Proteínas de Unión al ADN/genética , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas Proto-Oncogénicas c-bcl-6 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
The RhoH/TTF (ARHH) gene encodes a new member of the Ras superfamily of small GTPases. The gene was identified by fusion to the BCL6/LAZ3 oncogene in an initially described t(3;4)(q27;p11) translocation in a non-Hodgkin's lymphoma cell line. The predicted amino acid sequence of the RhoH/TTF gene product includes Rho-like GTPase structural motifs. The RhoH/TTF gene is restrictively expressed in hematopoietic cells and tissues. Mutations in the human RAS genes have been shown previously to be tumorigenic; in the search for a potential implication of the RhoH/TTF gene in hemopoietic malignancies, we established its genomic structure. The RhoH/TTF gene spans 35 kb and contains two exons, with the second bearing the entire amino-acid-coding region. Chromosomal mapping, by FISH experiments, places the RhoH/TTF gene on the short arm of chromosome 4, band p13.