{
  "abstract": "Background and Aims: APOBEC-associated mutagenesis is prominent in esophageal squamous cell carcinoma (ESCC), but genomic features associated with its intertumoral variability remain incompletely characterized. We investigated genomic correlates of APOBEC-associated mutagenesis while accounting for the compositional structure of mutational signature data. Methods: Mutational signatures were analyzed in 552 ESCC tumors from eight countries. APOBEC-associated mutagenesis was quantified as SBS2 plus SBS13 using absolute mutation counts and proportional contributions. Associations with co-occurring mutational signatures, total SBS burden, recurrent driver-gene alterations, and country were evaluated using correlation, sensitivity, and multivariable analyses. Principal component and regression-model robustness were additionally assessed. Results: APOBEC burden varied markedly across tumors (median, 2,002 mutations; IQR, 987-4,346). Several associations observed using signature proportions were not maintained in absolute-count analyses: SBS1, SBS3, and SBS5 changed direction, indicating sensitivity to compositional representation. In contrast, SBS18 remained inversely associated with APOBEC-associated mutagenesis in all variable pairings examined: proportion versus proportion (Spearman rho = -0.527), APOBEC proportion versus SBS18 absolute count (r = -0.435), and absolute count versus absolute count (Pearson r = -0.319, P = 1.59 x 10^-14; Spearman rho = -0.317). These are distinct comparisons rather than discrepant estimates. Notably, this cohort-wide relationship was primarily characterized by higher APOBEC burden in SBS18-negative than SBS18-positive tumors rather than a continuous inverse relationship among SBS18-positive tumors. The multivariable model had an in-sample R^2 of 0.400 but lower and variable 10-fold cross-validated performance (mean R^2 = 0.273). Country added little explanatory information to this model (delta R^2 = 0.008; global P = 0.402). ZNF750-mutant tumors had higher APOBEC burden than wild-type tumors (BH-FDR q = 0.0032), although only 12 tumors carried ZNF750 alterations. Conclusion: Genomic correlates of APOBEC-associated mutagenesis in ESCC are sensitive to the representation of mutational signature activity. SBS18 showed the most consistent inverse association, whereas the ZNF750 association warrants independent validation.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cape Coast"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "E. O. Ansah"
    },
    {
      "name": "J. A. Yentumi"
    },
    {
      "name": "E. Y. Kodom"
    },
    {
      "name": "P. O. Mensah"
    },
    {
      "name": "K. Fosu"
    },
    {
      "name": "I. K. Adu"
    },
    {
      "name": "E. A. Boahen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/45cs65rwqknnx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762354",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762354v1.full",
  "id": "45cs65rwqknnx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762354v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762354v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/45cs65rwqknnx.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:20:58Z",
      "native_id": "10.64898/2026.10.27.762354",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762354v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Genomic Correlates of APOBEC-Associated Mutagenesis in Esophageal Squamous Cell Carcinoma",
  "title_text": "Genomic Correlates of APOBEC-Associated Mutagenesis in Esophageal Squamous Cell Carcinoma",
  "type": "preprint",
  "updated_at": "2026-11-02T00:21:21Z",
  "url": "https://research.draconitic.com/paper/45cs65rwqknnx",
  "venue": "bioRxiv",
  "versions": []
}