Detection of PI3K Gene Mutations in Endometrial Cancer in Iran
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 phosphatidyl...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | fas |
| Published: |
Isfahan University of Medical Sciences
2012-03-01
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| Series: | مجله دانشکده پزشکی اصفهان |
| Subjects: | |
| Online Access: | http://jims.mui.ac.ir/index.php/jims/article/view/1350 |
| Summary: | 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. |
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| ISSN: | 1027-7595 1735-854X |