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一项荧光原位杂交研究:肺鳞状细胞癌中3q处的广泛扩增模式

A broad amplification pattern at 3q in squamous cell lung cancer--a fluorescence in situ hybridization study.

作者信息

Kettunen E, el-Rifai W, Björkqvist A M, Wolff H, Karjalainen A, Anttila S, Mattson K, Husgafvel-Pursiainen K, Knuutila S

机构信息

Department of Medical Genetics, Haartman Institute, Helsinki, Finland.

出版信息

Cancer Genet Cytogenet. 2000 Feb;117(1):66-70. doi: 10.1016/s0165-4608(99)00146-6.

Abstract

Frequent DNA copy number gain at 3q, with minimal overlapping area at 3q24-qter, has previously been reported in squamous cell carcinoma of the lung (SQCC), implicating the importance of genes at 3q in the tumorigenesis of SQCC. To further characterize the gain of DNA sequences at 3q, we performed interphase fluorescence in situ hybridization (FISH) analysis on 16 paraffin-embedded SQCC tumor samples that had previously been studied by comparative genomic hybridization (CGH). Eleven yeast artificial chromosome (YAC) probes located at 3q25-q27 and a chromosome 3-specific centromeric probe were used in the analysis. All SQCC tumors showed increase in DNA sequence copy number with 9-11 probes. In 5 tumors (31%) the number of centromeric signals varied from 3 to 5 and the YAC/centromeric signal ratio was 1.0, suggesting that the increase in DNA sequence copy number at 3q in these cases resulted from polysomy of chromosome 3. In 11 tumors (69%), the YAC/centromeric signal ratio varied between 1.5 and 4.7, indicating that the increase in DNA sequence copy number was due to intrachromosomal gain of DNA sequences at 3q. In each case, several YACs showed increased number of signals, demonstrating that the gained area was relatively large. Our findings therefore suggest that multiple genes located at 3q25-q27 are involved in the tumorigenesis of SQCC.

摘要

此前已有报道称,在肺鳞状细胞癌(SQCC)中,3q区域频繁出现DNA拷贝数增加,且在3q24 - qter区域重叠面积最小,这表明3q区域的基因在SQCC的肿瘤发生过程中具有重要作用。为了进一步明确3q区域DNA序列增加的特征,我们对16个先前已通过比较基因组杂交(CGH)研究过的石蜡包埋的SQCC肿瘤样本进行了间期荧光原位杂交(FISH)分析。分析中使用了位于3q25 - q27的11个酵母人工染色体(YAC)探针和一个3号染色体特异性着丝粒探针。所有SQCC肿瘤的9 - 11个探针显示DNA序列拷贝数增加。在5个肿瘤(31%)中,着丝粒信号数量在3至5之间变化,YAC/着丝粒信号比值为1.0,这表明在这些病例中3q区域DNA序列拷贝数的增加是由于3号染色体多体性所致。在11个肿瘤(69%)中,YAC/着丝粒信号比值在1.5至4.7之间变化,表明DNA序列拷贝数的增加是由于3q区域DNA序列的染色体内增加。在每种情况下,几个YAC显示信号数量增加,表明增加的区域相对较大。因此,我们的研究结果表明,位于3q25 - q27的多个基因参与了SQCC的肿瘤发生。

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