Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites: implications for clonal evolution
| Autor: | Paolo Casali, Hong Zan, Daniel M. Knowles, Andrea Cerutti, Hideyuki Ikematsu, Wataru Ikematsu |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Somatic cell Immunology Molecular Sequence Data Gene Rearrangement B-Lymphocyte Heavy Chain Genes myc Immunoglobulin Variable Region Somatic hypermutation Bone Marrow Cells Biology Somatic evolution in cancer Proto-Oncogene Mas Immunoglobulin kappa-Chains Antigen Gene Frequency Testicular Neoplasms medicine Immunology and Allergy Gene Rearrangement B-Lymphocyte Light Chain Humans Point Mutation Amino Acid Sequence Gene B cell Lymphoma AIDS-Related Genetics B-Lymphocytes Oncogene Base Sequence Cell Differentiation General Medicine Molecular biology Burkitt Lymphoma Clone Cells Binomial Distribution medicine.anatomical_structure Immunoglobulin Joining Region Orbital Neoplasms Bone marrow Immunoglobulin Heavy Chains Antibody Diversity |
| Zdroj: | Human immunology. 61(12) |
| ISSN: | 0198-8859 |
| Popis: | To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. Testis and orbit B cells expressed differentially mutated but collinear V(H)DJ(H), V kappa J kappa and c-myc gene sequences. Shared mutations accounted for 10.2%, 8.4%, and 4.3% of the overall V(H)DJ(H), V kappa J kappa, and c-myc gene sequences. Tumor-site specific V(H)DJ(H), V kappa J kappa, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc DNA. Both shared and tumor site-specific V(H)DJ(H), V kappa J kappa, and c-myc mutations displayed predominance of transitions over transversions. The "neoplastic" V(H)DJ(H) sequence was expressed by about 10(-5) cells in the bone marrow, and contained two of the three orbital, but none of the testicular V(H)DJ(H) mutations. The nature and distribution of the Ig V(D)J mutations found in the kappa chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets V(H)DJ(H), V kappa J kappa, and c-myc genes with comparable efficiency and modalities. |
| Databáze: | OpenAIRE |
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