Levy S, Mendel E, Kon S, Avnur Z, Levy R
Division of Oncology, Stanford University School of Medicine, California 94305.
J Exp Med. 1988 Aug 1;168(2):475-89. doi: 10.1084/jem.168.2.475.
The genes coding for the Ig light chains expressed in two cases of human follicular lymphoma were cloned and sequenced. In each case, multiple independent isolates of the tumor population were compared. Although each tumor represented a single clone of B cells with a unique V/J joint, different cells within each tumor had accumulated multiple point mutations in the V gene during clonal expansion. Most of the mutations observed were silent, but some resulted in amino acid replacements. Identical silent mutations were often observed in independent isolates of each tumor. By combining the current data with VH sequences obtained previously from the same cells, it was apparent that the repetitive silent mutations could not be explained solely by a genealogic tree. Such mutations could represent hot spots whose tendency to mutate may be influenced by neighboring DNA sequences or by the methylation of specific cytosine residues.
对两例人类滤泡性淋巴瘤中表达的免疫球蛋白轻链编码基因进行了克隆和测序。在每例病例中，对肿瘤群体的多个独立分离株进行了比较。尽管每个肿瘤代表具有独特V/J连接的单个B细胞克隆，但每个肿瘤内的不同细胞在克隆扩增过程中V基因积累了多个点突变。观察到的大多数突变是沉默的，但有些导致了氨基酸替换。在每个肿瘤的独立分离株中经常观察到相同的沉默突变。通过将当前数据与先前从相同细胞获得的VH序列相结合，很明显重复的沉默突变不能仅用系谱树来解释。此类突变可能代表热点，其突变倾向可能受相邻DNA序列或特定胞嘧啶残基甲基化的影响。
