Nielsen J L, Walsh J T, Degen D R, Drabek S M, McGill J R, von Hoff D D
Institute for Cancer Research and Care, San Antonio, Texas 78229.
Cancer Genet Cytogenet. 1993 Feb;65(2):120-4. doi: 10.1016/0165-4608(93)90219-c.
Amplification of cellular proto-oncogenes, important in tumor progression, has been correlated with a poor clinical outcome in a variety of human tumor types. Amplified genes are observed in two cytogenetically distinct entities, double minutes (DMs) and homogeneously staining regions (HSR). We examined 54 fresh lung tumor specimens obtained from patients with non-small cell lung cancer for cytogenetic evidence of gene amplification in the form of DMs. The majority of these patients had received no prior treatment. The cells were harvested within 24 hours after receiving the specimens, and the slides were stained with Giemsa to specifically look for DMs. We found DMs in 24 of 31 (77%) specimens that exhibited metaphase spreads. Similar incidences of DMs were found when histologic cell types, primary vs. non-primary tumors, and specimens from patients with prior treatment vs. no prior treatment were compared. Therefore, DMs occur frequently in non cultured lung tumor cells, providing evidence that gene amplification may be an important aspect of tumor behavior in patients with non-small cell lung carcinoma. Further investigation is warranted to identify the specific tumor-related genes located on these abnormal chromosomes. This also suggests that ongoing efforts to eliminate amplified drug-resistant genes or oncogenes contained on DMs in tumor cells may be relevant in patients with non-small cell lung cancer.
细胞原癌基因的扩增在肿瘤进展中很重要,并且在多种人类肿瘤类型中与不良临床结果相关。在两种细胞遗传学上不同的实体——双微体(DMs)和均匀染色区(HSR)中观察到扩增基因。我们检查了54份从非小细胞肺癌患者获取的新鲜肺肿瘤标本,以寻找DMs形式的基因扩增的细胞遗传学证据。这些患者中的大多数此前未接受过治疗。在收到标本后24小时内收获细胞,玻片用吉姆萨染色以专门寻找DMs。在31份呈现中期分裂相的标本中的24份(77%)中发现了DMs。当比较组织学细胞类型、原发肿瘤与非原发肿瘤以及来自接受过治疗与未接受过治疗患者的标本时,发现了相似的DMs发生率。因此,DMs在未培养的肺肿瘤细胞中频繁出现,这证明基因扩增可能是非小细胞肺癌患者肿瘤行为的一个重要方面。有必要进行进一步研究以鉴定位于这些异常染色体上的特定肿瘤相关基因。这也表明,正在进行的消除肿瘤细胞中DMs上所含扩增耐药基因或癌基因的努力可能与非小细胞肺癌患者相关。