---
title: "Pan-cancer catalog maps mutation enrichment at transcription factor binding sites"
id: "biorxiv-11-a-pan-cancer-catalog-of-mutagenesis-at-transcription-factor-binding-sites"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-11-a-pan-cancer-catalog-of-mutagenesis-at-transcription-factor-binding-sites"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.19.760246v1?rss=1"
published_at: "2026-10-20T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pan-cancer catalog maps mutation enrichment at transcription factor binding sites
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-11-a-pan-cancer-catalog-of-mutagenesis-at-transcription-factor-binding-sites
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.19.760246v1?rss=1)
- **Published At:** 2026-10-20T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study aggregated somatic mutations from over **4,000 tumors** spanning **15 tissue types**, constructing a pan-cancer resource of mutational patterns at transcription factor binding sites. - Investigators evaluated binding sites for **655 TFs**, grouped into **276 motif clusters**, and tested mutation enrichment at single-nucleotide resolution while accounting for sequence-dependent and local background variation. - Nearly one third of the analyzed pairs with sufficient mutation counts showed significant enrichment at one or more binding site positions, the authors reported. - Enrichment was most widespread in **melanoma**, but present across all 15 tissue types; the affected TFs and specific binding-site positions varied by tissue. - The cohort showed a correlation between TF expression level and enrichment: highly expressed TFs were more likely to display mutation enrichment than lowly expressed TFs, suggesting a role for binding in localized mutagenesis. - Mutational signature analysis implicated several processes beyond UV damage, including age-associated signatures, deamination lesions, oxidative damage, and tobacco-related processes, according to the authors. - The catalog identifies position-specific enrichment of **somatic mutations** at binding sites and pairs those positions with candidate mutagenic processes, providing targets for mechanistic follow-up. - The source did not report experimental validation details, specific numerical thresholds for ‘‘sufficient mutation counts,’’ or per-cluster sample sizes; those methodological specifics are not provided in the abstract and would require consulting the full manuscript or supplementary materials.
## Clinical Analysis & Structured Key Points
A pan-cancer catalog of mutagenesis at transcription factor binding sites | bioRxiv Skip to main content New Results A pan-cancer catalog of mutagenesis at transcription factor binding sites View ORCID Profile Harshit Sahay , View ORCID Profile Yuncheng Duan , View ORCID Profile Raluca Gordan doi: https://doi.org/10.64898/2026.10.19.760246 Harshit Sahay 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Harshit Sahay Yuncheng Duan 2 University of Massachusetts Chan Medical School Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yuncheng Duan Raluca Gordan 2 University of Massachusetts Chan Medical School Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Raluca Gordan For correspondence: raluca.gordan{at}umassmed.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Transcription factor (TF) binding can contribute to mutagenesis by altering DNA damage formation or interfering with DNA repair. Although these effects have been characterized for selected TFs and mutagenic processes, their prevalence across TFs and cancer types remains poorly understood. A systematic characterization of mutation enrichment at TF binding sites is needed to guide mechanistic studies and improve the interpretation of noncoding mutations in cancer. Here, we analyzed somatic mutations from over 4,000 tumors across 15 tissue types to generate a pan-cancer catalog of mutation patterns at binding sites for 655 TFs, organized into 276 motif clusters. We assessed mutation enrichment at single-nucleotide resolution, accounting for sequence-dependent and local variation in background mutation rates. Nearly one third of pairs with sufficient mutation counts showed significant enrichment at one or more binding site positions. Enrichment was most widespread in melanoma but was detected in all 15 tissue types, with the affected TFs and binding site positions varying across tissues. Highly expressed TFs were more likely to show enrichment than lowly expressed TFs, consistent with a role for TF binding in increased mutagenesis at the binding sites. Mutational signature analysis implicated processes beyond UV damage, including age-associated processes, deamination lesions, oxidative damage, and tobacco exposure, as potentially contributing to TF-induced mutagenesis. Together, these findings suggest that diverse interactions between TF binding, DNA damage, and DNA repair may contribute to mutation enrichment in regulatory DNA. Our pan-cancer catalog reveals position-specific enrichment of somatic mutations at TF binding sites across all 15 tissue types analyzed. By identifying specific TFs and binding site positions enriched for somatic mutations, together with potential mutagenic processes acting at these positions, our study provides a roadmap for experimental assessment of TF-induced mutagenesis and informs the interpretation and prioritization of non-coding mutations in cancer. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared U.S. National Science Foundation, https://ror.org/021nxhr62 , 2529591 National Institutes of Health, https://ror.org/01cwqze88 , R01-GM135658 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted October 20, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. 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