Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer

Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer
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DOI:
10.1097/01.coc.0000045920.49210.7a
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发表时间:
2004-02-01
影响因子:
2.6
通讯作者:
Fernández-Peralta, AM
Fernández-Peralta, AM
中科院分区:
医学4区
文献类型:
--
作者:
González-Aguilera, JJ;Oliart, S;Fernández-Peralta, AM

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尽管K-ras基因第12位密码子突变和TP 53基因突变是结直肠癌中常见的异常,但结合K-ras基因突变和TP 53基因突变进行结直肠癌诊断和预后判断仍存在争议。我们通过聚合酶链反应和测序分析了77例散发性结直肠腺癌中的K-ras和TP 53突变。我们观察到K-ras和TP 53突变之间呈负相关。K-ras基因突变但TP 53基因未突变的患者的生存率低于TP 53基因突变但K-ras基因未突变的患者。此外,我们发现K-ras和TP 53突变的患者预后最差。这些结果可能与先前发表的关于原代人类和啮齿动物细胞的数据有关,其中Ras的转化需要一个协同的癌基因或肿瘤抑制因子(如p53或p16)的失活。总之,K-ras和TP 53同时突变提示散发性结直肠癌预后较差。
Despite the fact that the mutations in K-ras codon 12 and TP53 are common abnormalities in colorectal cancer, the determination of K-ras mutation combined with TP53 gene mutation, with diagnostic and prognostic purposes is still controversial. We have analyzed K-ras and TP53 mutations in 77 sporadic colorectal adenocarcinomas by means of polymerase chain reaction and sequencing. We observed a negative correlation between both K-ras and TP53 mutations. Patients with mutations in K-ras but not in TP53 exhibited worse survival rates than those with mutations in TP53 and not in K-ras. Moreover, we found the worst outcome in patients with mutations in both K-ras and TP53. These results may relate to the previously published data about primary human and rodent cells, in which transformation by Ras require either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. In conclusion, simultaneous mutations in K-ras and TP53 are indicative of a worse prognosis in sporadic colorectal cancer.