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Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma
Abstract
The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutio…
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“RhoH was initially defined as a fusion partner and subject to somatic hypermutation in B cell lymphomas, although the biological relevance of RhoH mutations, which are mainly found in non-coding regions in these diseases, has never been defined (4 -6, 14, 15, 52).”
From A Unique Carboxyl-terminal Insert Domain in the Hematopoietic-specific, GTPase-deficient Rho GTPase RhoH Regulates Post-translational Processing (2013) · cites this paper as [14]
In the citing paper
“the 5’-noncoding region of the RHOH gene is a target of somatic hypermutation in a variety of B lymphoid malignancies such as diffuse large B-cell lymphomas(13, 14), AIDS-related non-Hodgkin lymphomas(15) and primary central nervous system lymphomas(16).”
From Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia (2010) · cites this paper as [15]
In the citing paper
“suggesting that RhoH protein levels may be critical for the survival of malignant B cells50,51,52.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [50]
In the citing paper
“RHOH mutations found in B cell lymphoma affect non-coding, presumably regulatory regions”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [50]
In the citing paper
“Mutations have been found in the 5′ non-coding region and 1st intron of the gene, suggesting an effect on the expression level of the protein14,67,68,31.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [67]
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Cited by
Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections
Crequer, A., Troeger, A., Patin, E., Ma, C. S., Picard, C., Pedergnana, V., Fieschi, C., Lim, A., Abhyankar, A., Gineau, L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62949 · Cited by 159
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Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders
Troeger, A., & Williams, D. A. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.07.002 · Cited by 73
Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia
Sanchez-Aguilera, A., Rattmann, I., Drew, D. Z., Müller, L. U. W., Summey, V, Lucas, D. M., Byrd, J. C., Croce, C. M., Gu, Y., Cancelas, J. A., et al. (2010) · Leukemia · doi:10.1038/leu.2009.217 · Cited by 52
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
RhoH Regulates Subcellular Localization of ZAP-70 and Lck in T Cell Receptor Signaling
Chae, H.-D., Siefring, J. E., Hildeman, D. A., Gu, Y., & Williams, D. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013970 · Cited by 35
The Role of RhoH in TCR Signalling and Its Involvement in Diseases
Ahmad Mokhtar, A. M., Hashim, I. F., Mohd Zaini Makhtar, M., Salikin, N. H., & Amin-Nordin, S. (2021) · Cells · doi:10.3390/cells10040950 · Cited by 25
Troeger, A., Chae, H.-D., Senturk, M., Wood, J., & Williams, D. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.505727 · Cited by 15
Galiègue‐Zouitina, S., Fu, Q., Carton‐Latreche, C., Poret, N., Cheok, M., Leprêtre, F., Figeac, M., Quesnel, B., El Bouazzati, H., & Shelley, C. S. (2021) · eJHaem · doi:10.1002/jha2.128 · Cited by 7
Metadata
- Authors
- Gaidano, G.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-09-01
- Volume
- 102
- Issue
- 5
- Pages
- 1833-1841
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 123
- References
- 0
- Language
- en
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