Erikson J, ar-Rushdi A, Drwinga H L, Nowell P C, Croce C M
Proc Natl Acad Sci U S A. 1983 Feb;80(3):820-4. doi: 10.1073/pnas.80.3.820.
We have previously demonstrated that translocations of V(H) genes from chromosome 14 to chromosome 8 and of the c-myc oncogene from chromosome 8 to chromosome 14 occur in Burkitt lymphomas with the t(8;14) chromosome translocation. An association of the c-myc gene with the C(mu) immunoglobulin gene has been observed in some but not all Burkitt lymphomas studied previously. In the present study, we have investigated the organization of the human heavy chain locus and of the c-myc gene in the P3HR-1 Burkitt lymphoma cell line. Becuase mouse/P3HR-1 somatic cell hybrids that retain only the 14q+ chromosome and no other human chromosome contain the human C(mu) and C(gamma) genes but not V(H) genes, we have concluded that the breakpoint on chromosome 14 in P3HR-1 cells is distal to C(mu) and between C(mu) and V(H). Thus, the breakpoint of human chromosome 14 differs in different Burkitt lymphoma cell lines. We also found that the human c-myc oncogene translocated to chromosome 14 in the P3HR-1 cell line is not recombined with the C(mu) gene. The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because we have observed DNA rearrangement of the c-myc gene with the C(mu) gene in only some of the Burkitt lymphoma cell lines studied elsewhere. Interestingly, high levels of transcripts of the c-myc oncogene were observed in Burkitt lymphomas with translocated c-myc oncogenes both rearranged and unrearranged. Therefore, the translocation of a c-myc oncogene to the heavy chain locus on human chromosome 14 is apparently sufficient for its transcriptional activation and may be an essential step in the pathway leading to neoplasia.
我们之前已经证明，在伴有t(8;14)染色体易位的伯基特淋巴瘤中，V(H)基因会从14号染色体易位至8号染色体，而c-myc癌基因会从8号染色体易位至14号染色体。在之前研究的部分但并非所有伯基特淋巴瘤中，已观察到c-myc基因与C(μ)免疫球蛋白基因存在关联。在本研究中，我们调查了P3HR-1伯基特淋巴瘤细胞系中人重链基因座和c-myc基因的组织情况。由于仅保留14q+染色体而无其他人类染色体的小鼠/P3HR-1体细胞杂种含有人类C(μ)和C(γ)基因，但不含V(H)基因，我们得出结论，P3HR-1细胞中14号染色体上的断点位于C(μ)远端，且在C(μ)和V(H)之间。因此，人类14号染色体的断点在不同的伯基特淋巴瘤细胞系中有所不同。我们还发现，P3HR-1细胞系中易位至14号染色体的人类c-myc癌基因并未与C(μ)基因发生重组。人类8号染色体上的断点在不同的伯基特淋巴瘤细胞系中可能也存在差异，因为我们在其他地方研究的部分伯基特淋巴瘤细胞系中才观察到c-myc基因与C(μ)基因的DNA重排。有趣的是，在c-myc癌基因发生易位且既有重排又有未重排情况的伯基特淋巴瘤中，均观察到了高水平的c-myc癌基因转录本。因此，c-myc癌基因易位至人类14号染色体上的重链基因座显然足以使其转录激活，这可能是导致肿瘤形成途径中的关键一步。
