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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The LAZ3/BCL6-RHOH gene fusion results in transcriptional deregulation of both genes.
“This results in the transcriptional deregulation of both genes [32].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [32]
The LAZ3/BCL6-RHOH gene fusion places LAZ3/BCL6 under control of the RHOH promoter instead of expressing a fusion protein, and reciprocally places RHOH under control of the LAZ3/BCL6 promoter.
“The breakpoint and gene orientation indicates that the gene fusion places LAZ3/BCL6 under the control of the RHOH promoter sequence instead of the expression of a fusion protein. Reciprocally, RHOH is placed under control of the LAZ3/BCL6 promoter.”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [32]
Most data gathered so far indicate that in human cancers the absence of a functional RhoH protein or reduced RhoH expression levels rather than its overexpression may play a role in pathogenesis.
“Most data gathered so far however indicate that in human cancers the absence of a functional RhoH protein or reduced RhoH expression levels rather than its overexpression may play a role in pathogenesis [32,56,57].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [32]
Cites
Chesi, M., Nardini, E., Brents, L. A., Schröck, E., Ried, T., Kuehl, W. M., & Bergsagel, P. L. (1997) · Nature Genetics · doi:10.1038/ng0797-260 · Cited by 637 · cited 1× · see citing works
“3 region, implicating the FGFR3 gene, which was shown to be deregulated by juxtaposition to the IgH gene, in this observation (Chesi et al., 1997).”
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The small GTPase RhoH is an atypical regulator of haematopoietic cells
Fueller, F., & Kubatzky, K. F. (2008) · Cell Communication and Signaling · doi:10.1186/1478-811x-6-6 · Cited by 40 · see citing works
RhoH GTPase: A Key Regulator of Hematopoietic Cell Proliferation and Apoptosis?
Gu, Y., Zheng, Y., & Williams, D. A. (2005) · Cell Cycle · doi:10.4161/cc.4.2.1395 · Cited by 20 · see citing works
- Authors
- Preudhomme, C., Roumier, C., Hildebrand, M. P., Dallery-Prudhomme, E., Lantoine, D., Laï, J. L., Daudignon, A., Adenis, C., Bauters, F., Fenaux, P., Kerckaert, J. P., & Galiègue-Zouitina, S.
- Affiliations
- Inserm (FR)
- Centre Hospitalier de Valenciennes (FR)
- Centre Oscar Lambret (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Venue
- Oncogene
- Published
- 2000-04-13
- Volume
- 19
- Issue
- 16
- Pages
- 2023-2032
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2325299883
- Cited by
- 135
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 3 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 5
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Rho GTP-binding proteins, non-Hodgkin lymphoma, multiple myeloma, chromosomal translocation, 14)(p13, fusion transcripts, hematologic malignancies, gene rearrangement
- MeSH terms
- Base Sequence, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 4, DNA-Binding Proteins, Female, Humans, Immunoglobulin Heavy Chains, Lymphoma, Non-Hodgkin, Middle Aged, Molecular Sequence Data, Multiple Myeloma, Translocation, Genetic, Blotting, Northern, Gene Rearrangement, In Situ Hybridization, Fluorescence, GTP-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, Proto-Oncogene Proteins c-bcl-6
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