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K-ras基因点突变:非小细胞肺癌中的一种稳定肿瘤标志物。

K-ras gene point mutation: a stable tumor marker in non-small cell lung carcinoma.

作者信息

Li S, Rosell R, Urban A, Font A, Ariza A, Armengol P, Abad A, Navas J J, Monzo M

机构信息

Department of Medical Oncology, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.

出版信息

Lung Cancer. 1994 Jul;11(1-2):19-27. doi: 10.1016/0169-5002(94)90279-8.

Abstract

K-ras gene point mutation is a highly frequent event in human malignancy. About one third of non-small cell lung cancer (NSCLC) patients harbor K-ras gene point mutational activations. This study investigates the prevalence of K-ras mutation in autopsy tumors with NSCLC, and the correlation of K-ras gene point mutations between primary tumors and metastases in NSCLC. Formalin-fixed, paraffin-embedded tissue sections of 15 primary lung tumors and their metastases, (obtained from autopsy), were examined for the presence of point mutations in K-ras gene codon 12, 13 and 61 by oligodeoxynucleotide hybridization analysis of DNA fragments, amplified by polymerase chain reaction (PCR). K-ras gene point mutations were detected in five cases of lung carcinoma, of which four were adenocarcinomas and one was squamous cell carcinoma. In each of these cases, identical K-ras gene mutations were found in the DNA of both the primary tumor and its corresponding distant metastases. Activating K-ras base-substitutions correlate well between the primary tumor and its corresponding metastases in NSCLC. In the negative cases where no K-ras mutation was found in the primary tumors, no newly acquired K-ras mutation appeared in the metastases. Our study indicates that K-ras point mutation serves as a stable tumor marker in NSCLC.

摘要

K-ras基因点突变在人类恶性肿瘤中是一种非常常见的事件。约三分之一的非小细胞肺癌(NSCLC)患者存在K-ras基因点突变激活。本研究调查了NSCLC尸检肿瘤中K-ras突变的发生率,以及NSCLC原发肿瘤与转移灶之间K-ras基因点突变的相关性。通过聚合酶链反应(PCR)扩增DNA片段,采用寡脱氧核苷酸杂交分析法检测了15例原发性肺肿瘤及其转移灶(取自尸检)的福尔马林固定、石蜡包埋组织切片中K-ras基因密码子12、13和61的点突变情况。在5例肺癌中检测到K-ras基因点突变,其中4例为腺癌,1例为鳞状细胞癌。在每例病例中,原发肿瘤及其相应远处转移灶的DNA中均发现相同的K-ras基因突变。在NSCLC中,原发肿瘤与其相应转移灶之间激活型K-ras碱基替换具有良好的相关性。在原发性肿瘤未发现K-ras突变的阴性病例中,转移灶未出现新获得的K-ras突变。我们的研究表明,K-ras点突变在NSCLC中可作为一种稳定的肿瘤标志物。

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