ArticleNature genetics2015
In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer.
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Analysis of PIK3CA mutation prevalence variation among colorectal cancer populations: a comprehensive review.Molecular biology reports · 2025Pooled it
- Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab.Cancer discovery · 2021Trial
- Trial
- Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations.American journal of hematology · 2016Trial
- Review
- Dual-oxygen pancreatic cancer organoids recapitulate basal-classical heterogeneity validated by spatial transcriptomics.British journal of cancer · 2026Article
- HER2 Heterogeneous Breast Cancer Models Reveal Novel Therapeutic Targets and Subclonal Dynamics during Evolution to Resistance to HER2-Targeted Therapies.Cancer discovery · 2026Article
- Strength through diversity: how cancers thrive when clones cooperate.Molecular oncology · 2026Review
- Tamoxifen induces PI3K activation in uterine cancer.Nature genetics · 2025Article
- Cell sorting based on single nucleotide variation enables characterization of mutation-dependent transcriptome and chromatin states.Nucleic acids research · 2025Article
- Transforming Cancer Care: Genomic Profiling, AI, and Next-Generation Drug Delivery Systems.Current genomics · 2025Review
- Development and validation of a multi-marker liquid bead array assay for the simultaneous detection ofHeliyon · 2024Article
- PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis.The Journal of clinical investigation · 2024Article
- Spatial analysis of recurrent glioblastoma reveals perivascular niche organization.JCI insight · 2024Article
- A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response.Cell reports. Medicine · 2024Article
- Spatial Biology of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- Recent advances in enzyme-free and enzyme-mediated single-nucleotide variation assayNational science review · 2024Review
- Mapping cancer biology in space: applications and perspectives on spatial omics for oncology.Molecular cancer · 2024Review
- Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.NPJ breast cancer · 2023Article
- Grading of lung adenocarcinomas with simultaneous segmentation by artificial intelligence (GLASS-AI).NPJ precision oncology · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Detection of minor, genetically distinct subpopulations within tumors is a key challenge in cancer genomics. Here we report STAR-FISH (specific-to-allele PCR-FISH), a novel method for the combined detection of single-nucleotide and copy number alterations in single cells in intact archived tissues. Using this method, we assessed the clinical impact of changes in the frequency and topology of PIK3CA mutation and HER2 (ERBB2) amplification within HER2-positive breast cancer during neoadjuvant therapy. We found that these two genetic events are not always present in the same cells. Chemotherapy selects for PIK3CA-mutant cells, a minor subpopulation in nearly all treatment-naive samples, and modulates genetic diversity within tumors. Treatment-associated changes in the spatial distribution of cellular genetic diversity correlated with poor long-term outcome following adjuvant therapy with trastuzumab. Our findings support the use of in situ single cell-based methods in cancer genomics and imply that chemotherapy before HER2-targeted therapy may promote treatment resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.