Haluska F G, Tsujimoto Y, Croce C M
Wistar Institute, Philadelphia, PA 19104.
Nucleic Acids Res. 1988 Mar 25;16(5):2077-85. doi: 10.1093/nar/16.5.2077.
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.
在伯基特淋巴瘤、未分化淋巴瘤（UL）及急性淋巴细胞白血病（ALL）病例中观察到的t(8;14)染色体易位，是分析得最为透彻的肿瘤特异性细胞遗传学异常之一。在此，我们对UL细胞系EW 36的克隆化(8;14)染色体断点进行分析。我们发现，参与易位的8号染色体区域位于此前已证实在地方性伯基特淋巴瘤断点簇附近，即MYC基因5'端约50 kb处。在那些病例中，我们证实V-D-J重组酶功能异常导致了易位。然而，在本病例中，易位的同种型转换机制被牵涉其中：在断点处，14号染色体上发现了Sμ/Sγ和Cγ序列。因此，EW 36 t(8;14)断点的特征与我们的B细胞淋巴瘤发生模型相符，该模型涉及引发恶性肿瘤的前体细胞、易位机制及肿瘤表型。
