B-101 Molecular genetics of HIV-associated B-cell lymphomas

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Molecular Genetics of HIV-associated B-cell Lymphomas Riccardo Dalla-Favera, MD Institute for Cancer Genetics Columbia University, New York, NY, 10032. Despite the immune reconstitution promoted by combined antiretroviral therapy (cART), lymphomas still represent the most common type of cancer in HIV- infected individuals. The most common lymphomas arising in HIV-infected individuals include Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL). Analogous to their counterparts occurring in immune-competent individuals, these malignancies derive from mature B cells involved in the germinal centers (GC), the site where antigen-stimulated B cells undergo selection for antigen affinity. The pathogenesis of these lymphomas is associated with genetic lesions, and preliminary studies based on limited cytogenetic and targeted gene analysis, have suggested some analogies with the genomic alterations (translocations involving the MYC and BCL6 oncogenes, and p53 inactivation) recurrently detected in non HIV-associated cases. While a comprehensive definition of the coding genome of both HIV-associated lymphomas is still lacking, whole-exome sequencing and copy number variation analysis has allowed the identification of a large number of recurrent genetic lesions in BL and DLBCL. These lesions have in turn identified recurrently altered cellular pathways that point to potential new therapeutic targets. These results will be reviewed as a guide to future comparative studies in HIV-associated lymphomas.

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