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Genetic Alterations in the K-Ras Gene Influence the Prognosis in Patients With Cervical Cancer Treated by Radiotherapy
  1. Pia Wegman, PhD*,
  2. Cecilia Ahlin, MD, PhD and
  3. Bengt Sorbe, MD
  1. * Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University; and
  2. Department of Gynecological Oncology, University Hospital, Örebro, Sweden.
  1. Address correspondence and reprint requests to Pia Wegman, PhD, University Hospital, Clinical Research Center, 70185 Örebro, Sweden. E-mail: pia.wegman{at}oru.se.

Abstract

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 radiochemotherapy, 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.

  • Cervical cancer
  • K-Ras
  • Mutation analysis
  • Prognostic factors

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Footnotes

  • The authors declare that they have no conflict of interest.