VanDevanter D R, Piaskowski V D, Casper J T, Douglass E C, Von Hoff D D
Tumor Institute, Swedish Hospital Medical Center, Seattle, Wash.
J Natl Cancer Inst. 1990 Dec 5;82(23):1815-21. doi: 10.1093/jnci/82.23.1815.
Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification.
成神经细胞瘤中原癌基因MYCN（也称为N - myc）的扩增已被证明与疾病分期和预后相关，但对于体内成神经细胞瘤中携带扩增MYCN基因的DNA结构知之甚少。我们利用DNA辐射和脉冲场凝胶电泳分析了来自不同患者的8例成神经细胞瘤（4例原发性肿瘤和4例表现出MYCN扩增的转移灶）中的MYCN扩增结构。8例成神经细胞瘤中有6例（3例原发性肿瘤和3例转移灶）表现出与环状染色体外DNA扩增结构存在相一致的MYCN DNA辐射图谱。5例成神经细胞瘤具有双微体染色体大小范围内的扩增结构，1例含有较小的DNA环。2例成神经细胞瘤表现出与较大（推测为染色体）扩增结构相一致的MYCN DNA辐射模式。在4例不同患者的成神经细胞瘤中观察到多种大小的DNA环，这意味着扩增结构在体内发生了多聚化。在所检测的8例成神经细胞瘤中有6例存在环状MYCN扩增结构，这表明环状DNA分子是体内基因扩增中的重要结构。
