ArticleCancer2013
High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma.
Article in Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Paired genomic profiling of primary tumor and lymph-node metastases identifies candidate prognostic features in penile squamous cell carcinoma.The oncologist · 2026Article
- Genomic and transcriptomic evaluation of primary and recurrent luminal B-like breast cancer.ESMO open · 2026Article
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- A network-based deep learning model integrating subclonal architecture for therapy response prediction in cancer.Cell reports methods · 2026Article
- Innovations in biomarker stratification for precision oncology.Clinical and experimental medicine · 2026Review
- Genomic signature driving preinvasive to invasive processes in stage I lung adenocarcinoma.International journal of cancer · 2026Article
- Fusobacterium nucleatum promotes tumor extravasation and metastasis in head and neck cancer via TLR4/MYB/ESPN axis.Communications biology · 2026Article
- Integrative Computational Analysis ofGenes · 2026Article
- Mechano-stress endorsing heterogeneous lung cancer cells migration into confined channels and investigating tumor spheroids growth of confined space migrating cells.Scientific reports · 2026Article
- Spatiotemporal Analysis of Molecular Continuity in Pathogenesis of Squamous Cell Carcinoma: From Normal Epithelium to Precancerous Lesions and Carcinoma.Cancer communications (London, England) · 2026Review
- Single-Cell Transcriptomic Profiling of GL261 Glioblastoma Cells Reveals Gene Expression Signatures Underlying Tumorigenicity.Cellular and molecular neurobiology · 2025Article
- Integrating MALDI-MSI-Based Spatial Proteomics and Machine Learning to Predict Chemoradiotherapy Outcomes in Head and Neck Cancer.International journal of molecular sciences · 2025Article
- Article
- Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer.The Journal of clinical investigation · 2025Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment.Biology · 2025Review
- A machine learning-derived angiogenesis signature for clinical prognosis and immunotherapy guidance in colon adenocarcinoma.Scientific reports · 2025Article
- Immunogenic cell death genes in single-cell and transcriptome analyses perspectives from a prognostic model of cervical cancer.Frontiers in genetics · 2025Article
- Integrated Analysis of Single-Cell RNA Sequencing and Machine Learning Reveals a T Cell-Specific PANoptosis Signature Predicting Prognosis and Immunotherapy in Prostate Cancer.Human mutation · 2025Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundAlthough the presence of genetic heterogeneity within the tumors of individual patients is established, it is unclear whether greater heterogeneity predicts a worse outcome. A quantitative measure of genetic heterogeneity based on next-generation sequencing (NGS) data, mutant-allele tumor heterogeneity (MATH), was previously developed and applied to a data set on head and neck squamous cell carcinoma (HNSCC). Whether this measure correlates with clinical outcome was not previously assessed.
methodsThe authors examined the association between MATH and clinical, pathologic, and overall survival data for 74 patients with HNSCC for whom exome sequencing was completed.
resultsHigh MATH (a MATH value above the median) was found to be significantly associated with shorter overall survival (hazards ratio, 2.5; 95% confidence interval, 1.3-4.8). MATH was similarly found to be associated with adverse outcomes in clinically high-risk patients with an advanced stage of disease, and in those with tumors classified as high risk on the basis of validated biomarkers including those that were negative for human papillomavirus or having disruptive tumor protein p53 mutations. In patients who received chemotherapy, the hazards ratio for high MATH was 4.1 (95% confidence interval, 1.6-10.2).
conclusionsThis novel measure of tumor genetic heterogeneity is significantly associated with tumor progression and adverse treatment outcomes, thereby supporting the hypothesis that higher genetic heterogeneity portends a worse clinical outcome in patients with HNSCC. The prognostic value of some known biomarkers may be the result of their association with high genetic heterogeneity. MATH provides a useful measure of that heterogeneity to be prospectively validated as NGS data from homogeneously treated patient cohorts become available.
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