EVIDENCE OF GENE AMPLIFICATION IN THE FORM OF DOUBLE MINUTE CHROMOSOMES IS FREQUENTLY OBSERVED IN LUNG-CANCER
EVIDENCE OF GENE AMPLIFICATION IN THE FORM OF DOUBLE MINUTE CHROMOSOMES IS FREQUENTLY OBSERVED IN LUNG-CANCER
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DOI：
10.1016/0165-4608(93)90219-c
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发表时间：
1993-02-01
影响因子：
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通讯作者：
VONHOFF, DD
中科院分区：
文献类型：
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作者：
NIELSEN, JL;WALSH, JT;VONHOFF, DD
细胞原癌基因的扩增在肿瘤进展中很重要，已与多种人类肿瘤类型的不良临床结局相关。 扩增的基因在两个细胞遗传学上不同的实体中观察到，双微体（DM）和均匀染色区域（HSR）。我们检查了54例非小细胞肺癌患者的新鲜肺肿瘤标本，以寻找DM形式的基因扩增的细胞遗传学证据。这些患者中的大多数既往未接受过治疗。在收到标本后24小时内收集细胞，用Giemsa染色玻片以特异性地寻找DM。我们在31个表现出中期扩散的标本中的24个（77%）中发现DM。当比较组织学细胞类型、原发性肿瘤与非原发性肿瘤以及既往接受过治疗与未接受过治疗的患者标本时，发现DM的发生率相似。因此，DM经常出现在非培养的肺肿瘤细胞中，这提供了证据表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。进一步的研究是必要的，以确定特定的肿瘤相关基因位于这些异常染色体。这也表明，正在进行的消除肿瘤细胞中DM上所含扩增的耐药基因或癌基因的努力可能与非小细胞肺癌患者相关。
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.