Detection of PI3K Gene Mutations in Endometrial Cancer in Iran

Document Type : Original Article (s)

Authors

1 Student, Department of Biology, School of Sciences, The Uneversity of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Biology, School of Sciences, The Uneversity of Isfahan, Isfahan, Iran

3 Associate Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Assistant Professor, Department of Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: The phosphatidylinositol-3-kinase (PI3K) signaling pathway regulates a variety of biological processes including proliferation, motility, insulin metabolism, and apoptosis. Activated PI3K phosphorylates phosphatidylinositol 4, 5 bisphosphate [PtdIns(4,5)P2] and thus produces phosphatidylinositol 3, 4, 5 triphosphate [PtdIns(3,4,5)P3]. This lipid activates Akt (protein kinase B). The frequency of PIK3 catalytic alpha (PIK3CA) gene mutations in endometrial cancer ranges from 24% to 39%. More than 90% of the mutations in PIK3CA have been localized in the helical (exon 9) and kinase (exon 20) domains.Methods: In this study, we analyzed the presence of PIK3CA mutations by means of single-strand conformational polymorphism (SSCP) and direct DNA sequencing in a population of Iranian endometrial cancer patients in the city of Isfahan and Tehran Cancer Institute. We also investigated the correlation between PIK3CA mutations and lymph node involvement, age, and disease stage and grade by Pearson's chi-square test.Findings: Among the 47% PIK3CA mutations in this study, 60% were identified in the kinase domain (exon 20). A novel mutation was found in codon 3059 of exon 20 [C3059T (A1020V)] which has not been reported previously in endometrial cancer.  In addition to hotspot mutation of exon 9 [G1624A (E542K)], we also detected a novel mutation [G1610A (R537Q)] in exon 9. We found that PIK3CA mutations are mainly associated with histological grade of tumors (P = 0.03; OR = 5.5). However, we did not observe any significant correlations between PIK3CA mutations and lymph node involvement, stage, or age of patients. Conclusion: Our results showed that the spectrum of PIK3CA mutations in our population was different. Therefore, further research on a larger number of samples and other types of cancers would be necessary.

Keywords

References

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Journal of Isfahan Medical School
Volume 29, Issue 150 - Serial Number 150
July and August 2011
Pages 1107-1113

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History

  • Receive Date: 18 September 2011
  • Revise Date: 25 May 2024
  • Accept Date: 06 April 2022

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