Siegelman M H, Cleary M L, Warnke R, Sklar J
J Exp Med. 1985 Apr 1;161(4):850-63. doi: 10.1084/jem.161.4.850.
Configurations of Ig gene DNA were examined in multiple biopsy specimens from seven cases of human B cell lymphoma that showed histologic differences among the specimens within each case. Analysis by Southern blot hybridizations with DNA probes for each of the three Ig loci revealed that the configurations of DNA within these loci were identical among the specimens in two of the cases. This result indicated the monoclonality of these lymphomas, despite differences in histology between biopsy specimens. In contrast, no common nongermline configurations of Ig gene DNA were detected among multiple biopsies in each of three other cases. Therefore, different histologies correlated with separate clones of proliferating B cells in these cases. In the last two cases, the configurations of light chain gene DNA were the same among biopsies in each case, consistent with a monoclonal origin in both lymphomas. However, differences were detected in the configuration of the heavy chain gene DNA. Analysis with a series of DNA probes of the mu heavy chain region indicated that the differences in the DNA configurations of the heavy chain genes from the biopsies probably arose from postrearrangement deletions of either the switch or constant regions of the mu gene. These studies indicate that, contrary to the conventional belief, individual tumors that contain different histologic types of lymphoma within the same patient frequently arise from separate clones of neoplastic cells. Furthermore, the heavy chain genes of monoclonal tumors may show postrearrangement deletions, often resulting from instability of DNA sequences within or around the mu switch region.
对7例人类B细胞淋巴瘤的多个活检标本进行了Ig基因DNA构型检测，这些病例中每个病例的标本在组织学上都存在差异。用针对三个Ig基因座的DNA探针进行Southern印迹杂交分析显示，其中2例病例的标本中这些基因座内的DNA构型相同。这一结果表明，尽管活检标本之间组织学存在差异，但这些淋巴瘤具有单克隆性。相比之下，在其他3例病例的多个活检标本中均未检测到Ig基因DNA的常见非胚系构型。因此，在这些病例中，不同的组织学与增殖B细胞的不同克隆相关。在最后2例病例中，每个病例的活检标本中轻链基因DNA的构型相同，这与两种淋巴瘤均起源于单克隆一致。然而，在重链基因DNA的构型中检测到了差异。用一系列μ重链区域的DNA探针分析表明，活检标本中重链基因DNA构型的差异可能源于μ基因转换区或恒定区的重排后缺失。这些研究表明，与传统观念相反，同一患者体内包含不同组织学类型淋巴瘤的单个肿瘤通常起源于肿瘤细胞的不同克隆。此外，单克隆肿瘤的重链基因可能显示重排后缺失，这通常是由于μ转换区内或其周围DNA序列的不稳定性所致。
