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

Cancer Research
|November 17, 2005
PubMed

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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