ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- FGFR4-associated APOBEC3 mutagenesis characterizes HER2-enriched subtype of human breast cancer.British journal of cancer · 2026Article
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- Aging, dauer, and stature phenotypes are conferred by structure-directed missense mutations in the endogenous AGE-1/phosphatidylinositol 3-kinase catalytic subunit.bioRxiv : the preprint server for biology · 2026Article
- PI3Kα Inhibitor and Degrader Inavolisib Can Co-opt FGFR2 to Enhance Responses in Patients with PIK3CA-Mutated Solid Tumors and in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- PI3K/Akt/mTOR pathway expression profiling reveals age- and subtype-specific molecular heterogeneity in the Nigerian breast cancer landscape.Frontiers in oncology · 2026Article
- Evolution and Co-occurrence of PI3K Pathway Gene Mutations in Endometrial Carcinoma Molecular Subtypes at the Single-Cell Level.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- UnveilingTranslational cancer research · 2025Article
- Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients.Cancers · 2025Article
- APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response.Frontiers in molecular biosciences · 2025Review
- The continually evolving landscape of novel therapies in oncogene-driven advanced non-small-cell lung cancer.Therapeutic advances in medical oncology · 2025Review
- Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations.The oncologist · 2024Article
- Green Synthesis of CuO Nanoparticles from MacroalgaeNanomaterials (Basel, Switzerland) · 2024Article
- Characterizing multi-PIK3CA mutations across cancer types: Toward precision oncology.Cancer medicine · 2024Article
- Basket Trials: Past, Present, and Future.Annual review of cancer biology · 2024Article
- Investigating the role of disulfidptosis related genes in radiotherapy resistance of lung adenocarcinoma.Frontiers in medicine · 2024Article
- STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts.Cancer discovery · 2023Article
- Integrative Analysis of a Large Real-World Cohort of Small Cell Lung Cancer Identifies Distinct Genetic Subtypes and Insights into Histologic Transformation.Cancer discovery · 2023Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeTo comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations and assess their impact on potential therapeutic outcomes. EXPERIMENTAL
designWe profiled a pan-cancer cohort comprised of 352,392 samples across 66 tumor types using a targeted hybrid capture-based next-generation sequencing panel covering at least 324 cancer-related genes. Molecularly defined subgroups, allelic configuration, clonality, and mutational signatures were identified and tested for association with PI3K inhibitor therapeutic response.
resultsMulti-PIK3CA mutations are found in 11% of all PIK3CA-mutant tumors, including 9% of low tumor mutational burden (TMB) PIK3CA-mutant tumors, and are enriched in breast and gynecologic cancers. Multi-PIK3CA mutations are frequently clonal and in cis on the same allele and occur at characteristic positions across tumor types. These mutations tend to be mutually exclusive of mutations in other driver genes, and of genes in the PI3K pathway. Among PIK3CA-mutant tumors with a high TMB, 18% are multi-PIK3CA mutant and often harbor an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational signature. Despite large differences in specific allele combinations comprising multi-PIK3CA mutant tumors, especially across cancer types, patients with different classes of multi-PIK3CA mutant estrogen receptor-positive, HER2-negative breast cancers respond similarly to PI3K inhibition.
conclusionsOur pan-tumor study provides biological insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations, with potential clinical utility to guide PI3K inhibition strategies.
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