Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas:: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study
Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas:: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study
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DOI：
10.1093/annonc/mdi908
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发表时间：
2005-05-01
影响因子：
50.5
通讯作者：
Russo, Antonio
中科院分区：
文献类型：
--
作者：
Bazan, V.;Agnese, V.;Russo, Antonio
背景：尽管 Ki-ras 和 TP53 突变可能是结直肠癌 (CRC) 进展中最广泛涉及和研究的基因异常，但它们在疾病复发和总体生存方面的意义尚未明确确定。 患者和方法：对来自连续 160 名既往未治疗患者的配对肿瘤和正常结肠组织样本进行了一项前瞻性研究，这些患者正在接受原发性可手术散发性 CRC 切除手术。测序后通过PCR-SSCP分析检测TP53（外显子5-8）和Ki-ras（外显子2）基因内的突变。结果：TP53基因外显子5至8的突变分析显示43%（68/160）的病例发生突变，而Ki-ras基因外显子2的突变分析显示46%（74/160）的病例发生突变。多变量分析显示，临床结果与单独 L3 结构域中特定 TP53 突变（仅在 DFS 中）或与密码子 13 处特定 Ki-ras 突变的组合密切相关。结论：单独 L3 结构域中特定 TP53 突变（仅在 DFS 中）或与密码子 13 处特定 Ki-ras 突变组合与散发性 CRC 的预后较差相关。
Background: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established.Patients and methods: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras ( exon 2) genes were detected by PCR-SSCP analyses following sequencing.Results: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% ( 68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% ( 74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone ( only in DFS) or in combination with specific Ki-ras mutations at codon 13.Conclusion: Specific TP53 mutations in L3 domain alone ( only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.