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Updated: Aug 14, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Mutation of the PIK3CA gene in anaplastic thyroid cancer
Ginesa García-Rostán1, Angela M Costa, Isabel Pereira-Castro
1Institute of Molecular Pathology and Immunology of Porto University, Porto, Portugal. grostan@ipatimup.pt
Abstract:
The phosphatidylinositol 3'-kinase (PI3K) pathway is frequently activated in thyroid carcinomas through the constitutive activation of stimulatory molecules (e.g., Ras) and/or the loss of expression and/or function of the inhibitory PTEN protein that results in Akt activation. Recently, it has been reported that somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%) among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors. Moreover, PIK3CA mutations have a tendency to cluster within the helical (exon 9) and the kinase (exon 20) domains. In this study, 13 thyroid cancer cell lines, 80 well-differentiated thyroid carcinomas of follicular (WDFC) and papillary (WDPC) type, and 70 anaplastic thyroid carcinomas (ATC) were investigated, by PCR-direct sequencing, for activating PIK3CA mutations at exons 9 and 20. Nonsynonymous somatic mutations were found in 16 ATC (23%), two WDFC (8%), and one WDPC (2%). In 18 of the 20 ATC cases showing coexisting differentiated carcinoma, mutations, when present, were restricted to the ATC component and located primarily within the kinase domain. Three cell lines of papillary and follicular lineage (K1, K2, and K5) were also found mutated. In addition, activation of Akt was observed in most of the ATC harboring PIK3CA mutations. These findings indicate that mutant PIK3CA is likely to function as an oncogene among ATC and less frequently well-differentiated thyroid carcinomas. The data also argue for a role of PIK3CA targeting in the treatment of ATC patients.
Insights
Activating mutations in PIK3CA were found in 23% of anaplastic thyroid carcinomas (ATC) and less frequently in well-differentiated thyroid carcinomas. These PIK3CA mutations may drive ATC development, suggesting PIK3CA as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The phosphatidylinositol 3'-kinase (PI3K) pathway is crucial in cell signaling and frequently dysregulated in various cancers.
- Somatic mutations in PIK3CA, a key PI3K catalytic subunit, are common in several tumor types, often affecting the helical and kinase domains.
Purpose of the Study:
- To investigate the frequency and location of activating PIK3CA mutations in thyroid carcinomas.
- To determine the potential role of PIK3CA mutations as oncogenes in anaplastic thyroid carcinoma (ATC) and well-differentiated thyroid carcinomas (WDTC).
Main Methods:
- PCR-direct sequencing was used to analyze exons 9 and 20 of the PIK3CA gene.
- The study included 13 thyroid cancer cell lines, 80 WDTC (follicular and papillary types), and 70 ATC.
- Akt activation was assessed in ATC samples with PIK3CA mutations.
Main Results:
- Activating PIK3CA mutations were identified in 23% of ATC, 8% of WDFC, and 2% of WDPC.
- In ATC with coexisting differentiated carcinoma, mutations were confined to the ATC component, primarily in the kinase domain.
- Akt activation was observed in most ATC harboring PIK3CA mutations.
Conclusions:
- Mutant PIK3CA likely functions as an oncogene in ATC and, less frequently, in WDTC.
- The findings support a role for PIK3CA in ATC pathogenesis.
- Targeting PIK3CA may represent a potential therapeutic strategy for ATC patients.
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