ArticleScientific reports2018
Distribution-based measures of tumor heterogeneity are sensitive to mutation calling and lack strong clinical predictive power.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- ITHindex: An integrated web-based platform for intratumor heterogeneity evaluation.PLOS digital health · 2026Article
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
- Deep learning image analysis quantifies tumor heterogeneity and identifies microsatellite instability in colon cancer.Journal of surgical oncology · 2023Article
- A compendium of co-regulated mitoribosomal proteins in pan-cancer uncovers collateral defective events in tumor malignancy.iScience · 2022Article
- Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden.Radiation oncology (London, England) · 2021Article
- Chromosomal copy number heterogeneity predicts survival rates across cancers.Nature communications · 2021Article
- Predicting survival of cancer patients by chromosomal copy number heterogeneity.Molecular & cellular oncology · 2021Article
- MCF7 Spheroid Development: New Insight about Spatio/Temporal Arrangements of TNTs, Amyloid Fibrils, Cell Connections, and Cellular Bridges.International journal of molecular sciences · 2020Article
- Prognostic significance of mutant-allele tumor heterogeneity in uterine corpus endometrial carcinoma.Annals of translational medicine · 2020Article
- Treating Cancer as an Invasive Species.Molecular cancer research : MCR · 2020Review
- Genetic heterogeneity and clonal evolution during metastasis in breast cancer patient-derived tumor xenograft models.Computational and structural biotechnology journal · 2020Article
- Assessing reliability of intra-tumor heterogeneity estimates from single sample whole exome sequencing data.PloS one · 2019Article
- Multi-Omic Analysis of Glioma Identifies RRM2 as a Prognostic Biomarker Associated With Tumor Stemness and Cell Cycle-Related Pathways.Technology in cancer research & treatmentArticle
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4 authors.
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Abstract
Mutant allele frequency distributions in cancer samples have been used to estimate intratumoral heterogeneity and its implications for patient survival. However, mutation calls are sensitive to the calling algorithm. It remains unknown whether the relationship of heterogeneity and clinical outcome is robust to these variations. To resolve this question, we studied the robustness of allele frequency distributions to the mutation callers MuTect, SomaticSniper, and VarScan in 4722 cancer samples from The Cancer Genome Atlas. We observed discrepancies among the results, particularly a pronounced difference between allele frequency distributions called by VarScan and SomaticSniper. Survival analysis showed little robust predictive power for heterogeneity as measured by Mutant-Allele Tumor Heterogeneity (MATH) score, with the exception of uterine corpus endometrial carcinoma. However, we found that variations in mutant allele frequencies were mediated by variations in copy number. Our results indicate that the clinical predictions associated with MATH score are primarily caused by copy number aberrations that alter mutant allele frequencies. Finally, we present a mathematical model of linear tumor evolution demonstrating why MATH score is insufficient for distinguishing different scenarios of tumor growth. Our findings elucidate the importance of allele frequency distributions as a measure for tumor heterogeneity and their prognostic role.
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