AIDSWEEKLY Plus; Monday, October 13, 2003
Staff Medical Writers

"The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes," researchers in New York noted. "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," explained G. Gaidano and colleagues at Columbia University.

"To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these four genes in various histologic subtypes," they wrote in the journal Blood.

"Mutations in one gene or more were detected in 19 of 39 (46.7%) 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)," study data indicated, "with 9 of 39 (23.1%) cases carrying mutations in two 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," test results revealed. "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 substitutions with likely functional consequences," according to the report. "Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases."

These findings demonstrate that "aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis," the researchers concluded.

Gaidano and coauthors published their findings in Blood (Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma. Blood. 2003 Sep 1;102(5):1833-41.

Additional information can be obtained by contacting G. Gaidano, Columbia University, Institute for Cancer Genetics, Russ Berrie Science Pavilion, 1150 St. Nicholas Avenue, Room 303, New York, NY 10032, USA.

The publisher of the journal Blood can be contacted at: American Society of Hematology, 1900 M Street NW, Suite 200, Washington, DC 20036, USA.

The information in this article comes under the major subject areas of AIDS & HIV, Genomics & Genetics, Hematology, Oncogenesis and Oncology.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Gaidano G, Pasqualucci L, Capello D, et al. "Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma", Blood. 2003 Sep 1;102(5):1833-41.

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