ArticleScientific reports2023
PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 23 citations in OpenAlex.
- Exceptional response to alpelisib in a heavily pretreated patient with metastatic breast cancer carrying a PIK3CA mutation outside SOLAR-1 eligible mutations: a case report.Acta oncologica (Stockholm, Sweden) · 2026Article
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- Correlation of the differential expression of PIK3R1 and its spliced variant, p55α, in pan-cancer.Molecular oncology · 2026Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.Communications chemistry · 2026Article
- ONCOPLEX: an oncology-inspired hypergraph model integrating diverse biological knowledge for cancer driver gene prediction.Scientific reports · 2026Article
- Case Report: Whole-genome sequencing of urothelial carcinoma in an adult patient with CLOVES syndrome reveals a lack ofFrontiers in oncology · 2026Article
- Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets.bioRxiv : the preprint server for biology · 2025Article
- DriverOmicsNet: an integrated graph convolutional network for multi-omics exploration of cancer driver genes.Briefings in bioinformatics · 2025Article
- Validation and analysis of key factors of Banxia Xiexin decoction against gastric cancer.World journal of gastrointestinal oncology · 2025Article
- Comprehensive genomic profiling of small bowel adenocarcinoma with liver metastasis.Journal of gastrointestinal oncology · 2025Article
- [Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- High Frequency ofCancers · 2025Article
- High frequency of the PIK3CA H1047L mutation in Indonesian breast cancer across molecular subtypes.PloS one · 2025Article
- Exploring breast cancer associated-gene panel for next-generation sequencing and identifying new, pathogenic variants in breast cancer from western China.Journal of Cancer · 2025Article
- Article
- Rare Drivers at Low Prevalence with High Cancer Effects in T-Cell and B-Cell Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Article
- Association ofmedRxiv : the preprint server for health sciences · 2023Article
- Article
- Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is little data concerning the implications of PIK3CA mutations outside of the known hotspots described in ER+/HER2- metastatic breast cancer (mBC). Similarly, PIK3R1 mutations could also lead to activation of PI3K pathway, but are poorly described. We determined the incidence and type of all somatic PIK3CA and PIK3R1 mutations by whole exome sequencing (WES) in a pan-cancer cohort of 1200 patients. Activation of the PI3K pathway was studied using phospho-AKT immunohistochemistry. Associations between PIK3CA/PIK3R1 mutations and response to chemotherapy were studied in mBC cases. We found 141 patients (11.8%) with a PIK3CA and/or PIK3R1 mutation across 20 different cancer types. The main cancer subtype was mBC (45.4%). Eighty-four mutations (62.2%) occurred in the three described hotspots; 51 mutations occurred outside of these hotspots. In total, 78.4% were considered activating or probably activating. Among PIK3R1 mutations, 20% were loss of function mutations, leading to a constitutional activation of the pathway. Phospho-AKT quantification in tumor samples was in favor of activation of the PI3K pathway in the majority of mutated tumors, regardless of mutation type. In ER+/HER2- mBC, first line chemotherapy efficacy was similar for PIK3CA-mutated and PIK3CA-WT tumors, whereas in triple negative mBC, chemotherapy appeared to be more effective in PIK3CA-WT tumors. In this large, real-life pan-cancer patient cohort, our results indicate that PIK3CA/PIK3R1 mutations are widely spread, and plead in favour of evaluating the efficacy of PI3K inhibitors outside of ER+/HER2- mBC and outside of hotspot mutations.
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