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Updated: Jul 10, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population
Jehad Abubaker1, Zeenath Jehan, Prashant Bavi
1Department of Human Cancer Genomic Research, King Fahad National Center for Children's Cancer and Research, King Faisal Specialist Hospital and Research Cancer, MBC#98-16, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Context:
Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC.
Objective:
The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC.
Design:
We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes.
Results:
PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs.
Conclusion:
A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.
Insights
Genetic alterations in PIK3CA and BRAF are common in Middle Eastern papillary thyroid cancer (PTC). These alterations, particularly BRAF mutations, are linked to advanced disease and poorer survival, suggesting targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently altered in human cancers.
- PIK3CA gene amplification occurs in some papillary thyroid cancer (PTC) cases, while mutations are less common in PTC compared to anaplastic thyroid carcinoma.
Purpose of the Study:
- To investigate genetic alterations including PIK3CA mutation and amplification, and RAS/RAF mutations in Middle Eastern PTC.
- To explore the association of these genetic alterations with clinicopathological characteristics.
Main Methods:
- Fluorescence in situ hybridization (FISH) for PIK3CA amplification analysis.
- Real-time quantitative PCR for validation of amplification.
- Direct DNA sequencing for PIK3CA, N2-RAS, and BRAF mutation analysis.
Main Results:
- PIK3CA amplification was observed in 53.1% of PTC cases.
- PIK3CA mutations (1.9%), N2-RAS mutations (6%), and BRAF mutations (51.7%) were identified.
- N-RAS mutations correlated with early stage and less extrathyroidal extension; BRAF mutations were associated with metastasis and poorer disease-free survival.
Conclusions:
- A high incidence of PIK3CA alterations and BRAF mutations suggests their significant role in Middle Eastern PTC tumorigenesis.
- The findings support the therapeutic targeting of the PI3K/AKT and MAPK pathways in PTC.
