The t(8;14) breakpoint of the EW 36 undifferentiated lymphoma cell line lies 5' of MYC in a region prone to involvement in endemic Burkitt's lymphomas.

AUTOR(ES)

Haluska, F G

RESUMO

One of the best analyzed tumor-specific cytogenetic abnormalities is the t(8;14) chromosomal translocation observed in cases of Burkitt's and undifferentiated lymphomas (ULs), and acute lymphoblastic leukemias (ALLs). Here we analyze the cloned (8;14) chromosomal breakpoint of the UL cell line EW 36. We show that the region of chromosome 8 involved in the translocation is situated near a site previously demonstrated to harbor a cluster of endemic Burkitt's lymphoma breakpoints, approximately 50 kb 5' of MYC. In those cases, we demonstrated that malfunction of the V-D-J recombinase generated the translocations. However, in this case the isotype switch mechanism of translocation is implicated: at the breakpoint, S mu/S gamma and C gamma sequences are found on chromosome 14. Thus, the features of the EW 36 t(8;14) breakpoint are consonant with our model for B-cell lymphomagenesis which relates the precursor cell that gives rise to malignancy, the mechanism of translocation, and the phenotype of the tumor.

Documentos Relacionados

• The t(8;14) chromosome translocation of the Burkitt lymphoma cell line Daudi occurred during immunoglobulin gene rearrangement and involved the heavy chain diversity region.
• Cloning and sequencing of a c-myc oncogene in a Burkitt's lymphoma cell line that is translocated to a germ line alpha switch region.
• Lambda Ig constant region genes are translocated to chromosome 8 in Burkitt's lymphoma with t(8;22).
• Three breakpoints of variant t(2;8) translocations in Burkitt's lymphoma cells fall within a region 140 kilobases distal from c-myc.
• Somatic mutation and transcriptional deregulation of myc in endemic Burkitt's lymphoma disease: heptamer-nonamer recognition mistakes?