Genetic Alterations in the K-Ras Gene Influence the Prognosis in Patients With Cervical Cancer Treated by Radiotherapy
Genetic Alterations in the K-Ras Gene Influence the Prognosis in Patients With Cervical Cancer Treated by Radiotherapy
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DOI：
10.1097/igc.0b013e3182049924
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发表时间：
2011-01-01
影响因子：
4.8
通讯作者：
Sorbe, Bengt
中科院分区：
文献类型：
--
作者：
Wegman, Pia;Ahlin, Cecilia;Sorbe, Bengt
在多种人类癌症中，K-Ras突变的发生率很高，特别是在密码子12，13和61中。然而，K-Ras突变在宫颈癌中的存在仍然存在争议。本研究的目的是调查K-Ras基因外显子1和2的可能突变，并评估K-Ras突变状态是否具有预后和预测意义，并与临床病理参数相关。我们检测了107例接受放化疗的宫颈癌患者的基因组DNA，以检测编码外显子1和2的突变，结果：11例患者（10%）存在K-Ras突变。7例肿瘤显示密码子59突变，3例肿瘤显示密码子38突变，1例肿瘤显示密码子13突变。在6例59位密码子突变的病例中，发现了65位密码子的额外改变，K-Ras突变患者的无复发生存率显著降低（P = 0.03），K-Ras状态与远处转移也有相关性（P = 0.04）。目前的数据表明，K-Ras突变在宫颈癌中相对少见，但与较差的预后相关，特别是在鳞状细胞癌的亚群中。宫颈癌需要新的标志物来改善个体化治疗，但K-Ras突变状态是否是这种情况下的潜在生物标志物，需要在更大的肿瘤系列和K-Ras基因的更多区域中进一步研究。
Introduction: A high incidence of K-Ras mutations has been identified in a variety of human cancers, especially in codon 12, 13, and 61. Nevertheless, the presence of K-Ras mutations in cervical cancer remains controversial. The aim of this study was to investigate possible mutations in exon 1 and 2 of the K-Ras gene and to assess whether K-Ras mutation status had prognostic and predictive significance and were linked to clinicopathological parameters.Methods: Genomic DNA from 107 patients with cervical cancer, treated with radio-chemotherapy, were examined for mutations in the coding exons 1 and 2, including exon/intron borders of the K-Ras gene using single-stranded conformation polymorphism and sequence analyses.Results: K-Ras mutations were detected in 11 patients (10%). Seven tumors showed a mutation in codon 59, 3 tumors in codon 38, and 1 tumor in codon 13. In 6 of the cases with a mutation in codon 59, an additional alteration located in codon 65 was found. Patients with K-Ras mutations had significantly worse recurrence-free survival (P = 0.03), and an association between K-Ras status and distant metastases was also seen (P = 0.04).Conclusions: The present data indicate that K-Ras mutations are relatively uncommon in cervical cancer but associates with poorer prognosis, especially in the subset of squamous cell carcinomas. There is a need for new markers in cervical cancer to improve individual treatment, but whether K-Ras mutation status is a potential biomarker in this situation needs further investigations in larger tumor series and in more regions of the K-Ras gene.