Phenotypic and Genotypic Lineage Switch of a Lymphoma with Shared Chromosome Translocation and T‐Cell Receptor γ Gene Rearrangement

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Abstract
A case of non‐Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T‐cell type, pleomorphic small cell lymphoma developed, followed by B‐cell type, diffuse centroblastic/centrocytic lymphoma, and finally T‐zone lymphoma without follicles again developed, from which AST‐1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B‐cell tumor, the second relapsed T‐cell tumor and AST‐1 cell line. Furthermore, T‐cell receptor (TCR) γ gene rearrangement bands of the same size were observed in the first relapsed B‐cell tumor and the second relapsed T‐cell tumor as well as AST‐1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR δ/α gene complex, was observed in the second relapsed tumor and AST‐1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR δ/α gene complex was studied. The result showed that two rearrangements of TCR α gene detected with Jα probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST‐1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.