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Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma

Jennifer Dunlap1, Claudia Le, Arielle Shukla

  • 1Department of Pathology, Oregon Health & Science University, L471, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.

Breast Cancer Research and Treatment
|May 7, 2009
PubMed

Insights

Key breast cancer genes phosphatidylinositol-3-kinase (PIK3CA) and AKT1 mutations occur early in tumor development. These mutations are present in both invasive and in situ breast carcinoma, impacting PI3 kinase pathway therapeutics.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Activated protein kinases are key therapeutic targets in breast cancer.
  • Mutations in phosphatidylinositol-3-kinase (PIK3CA) occur in 8-40% of invasive breast carcinomas, and AKT1 mutations in 1-8%.

Purpose of the Study:

  • To investigate the presence and timing of PIK3CA and AKT1 mutations in breast precursor lesions.
  • To understand the molecular evolution of breast tumorigenesis.

Main Methods:

  • Macrodissection of formalin-fixed paraffin-embedded invasive breast carcinoma with in situ components.
  • Screening for PIK3CA (exons 7, 9, 20) and AKT1 (exon 2) mutations.
  • Laser capture microdissection (LCM) to compare genotypes of invasive and in situ tumor cells.

Main Results:

  • 14.8% (12/81) of invasive carcinomas harbored PIK3CA mutations (exon 20: 7 H1047R, 1 H1047L; exon 9: 2 E545K, 1 E542K, 1 E545G).
  • 3.8% (3/78) of invasive carcinomas had AKT1 E17K mutations.
  • Identical PIK3CA and AKT1 mutations were found in matched invasive and in situ tumor components in all informative cases.
  • Mutational status did not correlate with clinical parameters (hormone receptor status, grade, lymph node status).

Conclusions:

  • PIK3CA and AKT1 mutations are early events in breast cancer development.
  • The presence of these mutations in both invasive and in situ lesions has significant implications for PI3 kinase pathway-targeted therapeutics.

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