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Updated: Sep 14, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

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

Published on: September 20, 2016

24.5K

Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation

Junkyu Kim1, Hye-Lim Jang2, Jung Young Hong1

  • 1Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.

Cancer Genetics
|July 19, 2025
PubMed
Abstract

Insights

PIK3CA mutations were found in 9.2% of 3886 patients, particularly in colorectal cancer. These mutations correlated with higher tumor mutation burden and microsatellite instability, offering insights into PIK3CA-driven solid tumors.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancers due to PIK3CA gene alterations.
  • While PIK3CA-mutated breast cancer shows treatment efficacy, other malignancies lack targeted therapies.
  • Understanding PIK3CA mutations and amplifications across diverse cancer types is crucial.

Purpose of the Study:

  • To investigate the incidence and spectrum of PIK3CA mutations and amplifications in a large cohort of patients with various solid tumors.
  • To explore the correlation between PIK3CA aberrations and key biomarkers such as tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD).

Main Methods:

  • Next-generation sequencing (NGS) using Trusight Oncology 500 was performed on 3886 patients across 36 cancer types.
  • Data analysis included the incidence of PIK3CA mutations and amplifications, their distribution by cancer type, and associations with TMB, MSI, and HRD.
  • Specific mutation sites were identified.

Main Results:

  • PIK3CA mutations were detected in 9.2% (358/3886) of patients, with the highest prevalence in colorectal cancer (52.8%).
  • Patients with PIK3CA mutations exhibited significantly higher TMB (31.8% vs. 12.5%) and MSI-high rates (7.8% vs. 1.6%) compared to those without (p=0.001).
  • PIK3CA amplifications occurred in 1.3% (51/3886), mainly in gastric, bladder, and colorectal cancers, and were linked to lower TMB, MSI-high, and HRD rates. Common mutation sites included E545K, E542K, and H1047R.

Conclusions:

  • This study provides a comprehensive overview of PIK3CA aberrations in metastatic solid tumors, identifying frequent mutations (9.2%) and amplifications (1.3%).
  • NGS analysis revealed significant associations between PIK3CA mutations and increased TMB/MSI-high status.
  • The findings enhance the understanding of PIK3CA alterations across various cancers, potentially guiding future therapeutic strategies.
Keywords:
AmplificationFusionPIK3CA aberrationPIK3CA inhibitorSingle nucleotide variants

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