Related Experiment Video

Updated: Aug 15, 2025

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
07:54

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence

Published on: October 25, 2011

18.7K

Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations

Smruthy Sivakumar1, Dexter X Jin1, Ruchita Rathod2

  • 1Foundation Medicine, Cambridge, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 3, 2023
PubMed
Abstract

Insights

Multiple PIK3CA mutations occur in 11% of PIK3CA-mutant cancers, particularly in breast and gynecologic tumors. These genetic alterations, while diverse, show similar responses to PI3K inhibitors in specific breast cancer subtypes.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • The PI3K/AKT/mTOR pathway is a critical regulator of cell growth and survival, frequently dysregulated in cancer.
  • PIK3CA gene mutations are common oncogenic drivers, but the implications of multiple mutations within the same gene (multi-PIK3CA) remain less understood.

Purpose of the Study:

  • To comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations.
  • To assess the impact of multi-PIK3CA mutations on potential therapeutic outcomes, particularly response to PI3K inhibitors.

Main Methods:

  • A pan-cancer cohort of 352,392 samples across 66 tumor types was profiled using next-generation sequencing.
  • Analysis included identification of molecular subgroups, allelic configuration, clonality, and mutational signatures.
  • Associations with PI3K inhibitor therapeutic response were tested.

Main Results:

  • Multi-PIK3CA mutations were found in 11% of PIK3CA-mutant tumors, enriched in breast and gynecologic cancers.
  • These mutations are often clonal, located on the same allele (in cis), and mutually exclusive of other driver or PI3K pathway genes.
  • Despite allelic diversity, multi-PIK3CA mutant ER+/HER2- breast cancers showed similar responses to PI3K inhibition.

Conclusions:

  • Pan-tumor analysis reveals biological insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations.
  • Findings highlight potential clinical utility for guiding PI3K inhibition strategies in specific cancer contexts.

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