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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors

Guojun Wu1, Elizabeth Mambo, Zhongmin Guo

  • 1Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA.

The Journal of Clinical Endocrinology and Metabolism
|June 2, 2005
PubMed
Abstract

Insights

PIK3CA gene mutations are rare in thyroid tumors. However, PIK3CA gene amplification is relatively common and may activate the phosphotidylinositol 3-kinase (PI3K)/Akt pathway in certain thyroid cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway is frequently overactivated in human cancers, including thyroid cancer.
  • The exact mechanisms driving PI3K/Akt pathway overactivation in thyroid cancer are not fully understood.

Purpose of the Study:

  • To investigate the role of the PIK3CA gene, a common driver of PI3K/Akt pathway activation in other cancers, in thyroid tumors.
  • To determine the frequency of PIK3CA gene mutations and amplification in various types of thyroid tumors.

Main Methods:

  • Genomic DNA was isolated from a cohort of thyroid tumors (benign adenomas, papillary, follicular, anaplastic, and medullary thyroid cancers) and cell lines.
  • Exons of the PIK3CA gene known for common mutations were sequenced.
  • Real-time quantitative PCR was used to assess PIK3CA gene amplification.
  • Fluorescence in situ hybridization and Western blotting were employed for validation in cell lines.

Main Results:

  • No significant PIK3CA gene mutations were detected across all tested thyroid tumor types and cell lines, except for a single nucleotide polymorphism in two cases.
  • PIK3CA gene amplification was observed in 12% of benign thyroid adenomas, 5% of papillary thyroid cancers, 24% of follicular thyroid cancers, and 71% of thyroid tumor cell lines.
  • Amplification correlated with Akt activation, confirmed by molecular analyses.

Conclusions:

  • Mutation of the PIK3CA gene is not a frequent event in thyroid tumorigenesis.
  • PIK3CA gene amplification represents a relatively common mechanism for activating the PI3K/Akt pathway in a subset of thyroid tumors.
  • This finding suggests PIK3CA amplification as a potential therapeutic target in specific thyroid cancer contexts.

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