Wong A J, Ruppert J M, Eggleston J, Hamilton S R, Baylin S B, Vogelstein B
Science. 1986 Jul 25;233(4762):461-4. doi: 10.1126/science.3014659.
The relationship of the copy numbers of the c-myc and N-myc oncogenes to tumor formation and progression was studied in small cell carcinoma of the lung. When 96 neoplastic lesions from 45 patients were examined, these lesions could be grouped into three categories: high copy (tumors with greater than 3 copies of the N-myc or c-myc gene per haploid genome), middle copy (1.5 to 3 copies per genome), and normal copy. Fourteen of the patients had middle copy tumors, but this was almost always a result of chromosome duplication rather than the amplification of a small genetic locus. In contrast, five patients had high copy tumors, with the increased copy number in each case due to gene amplification. The amplification did not occur in a heterogeneous fashion within individual patients, since all metastatic lesions from patients with high copy lung tumors were also high copy, while none of 41 metastatic lesions from the other patients were high copy. These data suggest that gene amplification is an important step in neoplastic growth in a subset of patients with small cell carcinoma of the lung and that this genetic event occurs relatively early (before metastasis) in this subset.
在肺小细胞癌中研究了c-myc和N-myc癌基因的拷贝数与肿瘤形成及进展的关系。当检查45例患者的96个肿瘤性病变时，这些病变可分为三类：高拷贝（每个单倍体基因组中N-myc或c-myc基因拷贝数大于3个）、中拷贝（每个基因组1.5至3个拷贝）和正常拷贝。14例患者有中拷贝肿瘤，但这几乎总是染色体复制的结果，而非小基因位点扩增。相比之下，5例患者有高拷贝肿瘤，每例中拷贝数增加均因基因扩增所致。基因扩增在个体患者中并非以异质性方式发生，因为高拷贝肺肿瘤患者的所有转移灶也都是高拷贝，而其他患者的41个转移灶均无高拷贝。这些数据表明，基因扩增是一部分肺小细胞癌患者肿瘤生长中的重要步骤，且这一基因事件在该亚组中相对较早（转移前）发生。
