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Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic

Libero Santarpia1, Adel K El-Naggar, Gilbert J Cote

  • 1Department of Endocrine Neoplasia and Hormonal Disorders, Unit 435, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030-4009, USA.

The Journal of Clinical Endocrinology and Metabolism
|November 9, 2007
PubMed
Abstract

Insights

Anaplastic thyroid carcinoma (ATC) involves mutations in BRAF and PIK3CA pathways, crucial for tumor progression and dedifferentiation. These genetic alterations are key drivers in thyroid cancer advancement.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Anaplastic thyroid carcinoma (ATC) may arise from differentiated thyroid carcinoma (DTC), indicating a malignant progression continuum.
  • The Ras/Raf-MAPK and PI3K/Akt pathways are vital in DTC but their role in ATC pathogenesis is unclear.

Purpose of the Study:

  • To investigate the involvement of Ras/Raf-MAPK and PI3K/Akt pathways in the development of ATC.
  • To identify specific gene mutations and copy number alterations associated with ATC.

Main Methods:

  • Analyzed BRAF, PIK3CA, PTEN, and RAS gene mutations in 36 ATC and 16 matched lymph node metastasis samples.
  • Assessed PIK3CA copy number gain using real-time quantitative PCR.
  • Performed immunohistochemistry for phospho-ERK and phospho-AKT.

Main Results:

  • BRAF V600E mutations found in 25% of ATCs, often shared with DTC components.
  • PIK3CA mutations occurred in 14% of ATCs, with copy number gains in 39%.
  • RAS and PTEN mutations were found in 6% of ATCs each.

Conclusions:

  • BRAF mutations contribute to a subset of ATC tumorigenesis and metastasis.
  • PIK3CA alterations are significant in later stages of ATC and thyroid cancer progression.
  • Activation of both pathways is implicated in ATC dedifferentiation.

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