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Mutation of the PIK3CA gene in ovarian and breast cancer

Ian G Campbell1, Sarah E Russell, David Y H Choong

  • 1VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. ian.campbell@petermac.org

Cancer Research
|November 3, 2004
PubMed

Insights

The phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast and ovarian cancers. PIK3CA mutations and amplifications are significant drivers in these cancers, particularly in specific ovarian cancer subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phosphatidylinositol 3'-kinases (PI3Ks) are crucial lipid kinases implicated in cancer development.
  • Previous research indicated frequent PIK3CA mutations in colorectal cancer, but its role in other cancers was less understood.
  • Limited tumor samples in prior studies hindered a comprehensive understanding of PIK3CA's relevance across diverse cancer types.

Purpose of the Study:

  • To investigate the frequency and significance of PIK3CA gene mutations and amplifications in a broad range of human tumors.
  • To determine the prevalence of PIK3CA alterations in breast and ovarian cancers.
  • To explore the association of PIK3CA mutations with specific histologic subtypes and clinical features in ovarian cancer.

Main Methods:

  • Screening of 284 primary human tumors for mutations across all coding exons of the PIK3CA gene.
  • Utilizing single-stranded conformational polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) for mutation detection.
  • Assessing PIK3CA gene amplification through quantitative analysis, with a threshold of >7-fold increase.

Main Results:

  • PIK3CA mutations were identified in 40% of 70 primary breast cancers, representing the most common mutation found in this cancer type.
  • In 167 primary epithelial ovarian cancers, 6.6% harbored PIK3CA mutations, with a significant association with endometrioid and clear cell subtypes (20%) compared to serous carcinomas (2.3%).
  • PIK3CA gene amplification occurred in 24.5% of ovarian cancers, inversely correlated with mutations, and PIK3CA alterations (mutation or amplification) were found in 30.5% of all ovarian cancers and 45% of endometrioid/clear cell subtypes.

Conclusions:

  • PIK3CA is a frequently mutated gene in breast cancer and an oncogene in ovarian cancer.
  • The study provides the first direct evidence of PIK3CA's oncogenic role in ovarian cancer.
  • Findings highlight the importance of PIK3CA alterations in breast and ovarian tumorigenesis, suggesting potential therapeutic targets.

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