PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers

Filip Janku1, J Jack Lee, Apostolia M Tsimberidou

  • 1Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Plos One
|August 11, 2011
PubMed
Abstract

Insights

Oncogenic mutations in PIK3CA, RAS (KRAS, NRAS), and BRAF genes are common in many cancers. These mutations often coexist, suggesting potential therapeutic targets in diverse tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oncogenic mutations in PIK3CA, RAS (KRAS, NRAS), and BRAF genes are frequently observed in various malignancies.
  • These mutations activate critical cancer-driving pathways, including the PI3K/AKT/mTOR and RAS/RAF/MEK pathways.

Purpose of the Study:

  • To investigate the frequency and co-occurrence of PIK3CA, RAS (KRAS, NRAS), and BRAF mutations in a diverse cohort of cancer patients.
  • To identify specific cancer types with high prevalence of these mutations.

Main Methods:

  • Tumor tissues from 504 patients with diverse cancers were analyzed.
  • Polymerase chain reaction-based DNA sequencing was employed to detect mutations in PIK3CA, KRAS, NRAS, and BRAF genes.

Main Results:

  • PIK3CA mutations were found in 11% of patients, KRAS in 19%, NRAS in 8%, and BRAF in 9%.
  • High mutation frequencies were observed in specific cancers: PIK3CA in cervical, uterine, breast, and colorectal cancers; KRAS in pancreatic, colorectal, and uterine cancers; NRAS in melanoma and uterine cancer; BRAF in melanoma and colorectal cancer.
  • PIK3CA mutations significantly co-occurred with RAS (KRAS, NRAS) and BRAF mutations (47% vs. 24%, p=0.001), and vice versa (28% vs. 10% for KRAS, p=0.001).

Conclusions:

  • Mutations in PIK3CA, RAS (KRAS, NRAS), and BRAF are prevalent across a wide spectrum of tumors.
  • A significant co-occurrence of PIK3CA mutations with RAS (KRAS, NRAS) and BRAF mutations was observed in diverse tumor types.

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