Refinement and precision in the classification of murine lymphomas by genotyping with immunoglobulin and T cell receptor probes.
Of 114 murine leukemia virus induced lymphomas and 12 lymphoid hyperplasias, T cell receptor beta-chain gene and immunoglobulin gene constellation (immunogenotype) was compared with histology and surface marker expression (immunomorphology). In 53 out of 114 lymphomas (45%), definite conclusions concerning cell lineage were possible only after genotyping. Fifteen follicular center cell lymphomas with a clear phenotype (13 tumors with B and 2 tumors with T cell markers) were genotypically classified in agreement with their phenotype. Of another 21 follicular center cell tumors (12 null cell tumors lacking T or B cell-specific antigens and 9 tumors phenotypically composed of mixtures of T and B cells), B cell lineage was determined upon genotyping in 17 cases. All 41 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a B cell phenotype, upon DNA analysis were indeed classified as T and B cell tumors, respectively. Of another 10 lymphoblastic tumors (phenotypically 4 null cell lymphomas, 6 mixtures of T and B cells) genotyping established lineage in 9 cases. Fifteen lymphoblastic neoplasms showing lineage infidelity because of simultaneous expression of a T (Thy-1) and a B cell (B220) marker were clearly of T cell genotype. Only 4 out of 114 lymphomas tested retained both Ig and T cell receptor genes in germline configuration, although 6 lymphomas in these series had both Ig and T cell receptor genes rearranged. Four of twelve lesions histologically classified as hyperplasias nevertheless contained a monoclonal B cell population at the DNA level. Immunogenotypic evaluation of lymphomas allows precise lymphoma lineage determination even in cases where marker analysis falls short, and is clearly superior in detecting mono- or oligoclonality in lymphomas versus polyclonality in benign lesions.
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics; D005803:Genes, Immunoglobulin; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D009052:Leukemia Virus, Murine; D008223:Lymphoma / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D007145:Immunoglobulin kappa-Chains; D011948:Receptors, Antigen, T-Cell