Genetic profile of 22 pancreatic carcinoma cell lines -: Analysis of K-ras, p53, p16 and DPC4/Smad4
Genetic profile of 22 pancreatic carcinoma cell lines -: Analysis of K-ras, p53, p16 and DPC4/Smad4
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DOI：
10.1007/s004280100474
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发表时间：
2001-12-01
期刊：
影响因子：
3.5
通讯作者：
Scarpa, A
中科院分区：
文献类型：
--
作者：
Moore, PS;Sipos, B;Scarpa, A
K-ras、p53、p16和DPC 4基因是胰腺导管癌中最常改变的基因。我们分析了22个细胞系，这些基因的改变，通过直接序列分析和甲基化特异性聚合酶链反应。这些细胞系显示K-ras和p53突变的频率分别为91%和95%。在所有病例中均发现了p16（INK 4a）的改变，其中包括9个纯合缺失，7个突变和6个病例中的启动子甲基化：8个细胞系（36%）具有DPC 4的改变，包括1个突变和7个纯合缺失。最典型的突变谱涉及K-ras、p53和p16（INK 4a），20例（91%）同时发生变异。Bight细胞系在所有四个基因中都有改变。DPC 4的失活总是伴随着所有其他三个基因的改变。关于胰腺癌细胞系中累积遗传改变的这一全面数据对于涉及可能与特定基因或分子途径失活相关的药物敏感性或耐药性的研究将具有重要价值。
The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. We analyzed 22 cell, lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. Alterations in p16(INK4a) were found in all cases and included nine homozygous deletions, seven mutations and promoter methylation in six cases: Eight cell lines (36%) had an alteration of DPC4, including one mutation and seven homozygous deletions. The most typical mutational profile involved K-ras, p53, and p16(INK4a), concurrently aberrated in 20 cases (91%). Bight cell lines had alterations in all four genes. Inactivation of DPC4 was always accompanied by alteration of all of the other three genes. This comprehensive data regarding the cumulative genetic alterations in pancreatic carcinoma cell lines will be of great value for studies involving drug sensitivity or resistance that may be associated with inactivation of a particular gene or molecular pathway.