Skip to content
DraconiticResearch
Search Sources API
186,086 studies31 sourcesUpdated 55 min ago
Peer-reviewedCC BYScientific Reports

Comprehensive characterization of DNA polymerases driver variants using large genomic dataset

  • Dana Dayan1
  • Hagay Ladany1
  • Fabian Glaser2
  • William D. Foulkes3
  • Yosef E. Maruvka1
  1. 1Department of Biotechnology and Food Engineering, Technion – Israel Institute of Technology
  2. 2Technion Center for Structural Biology, Technion – Israel Institute for Technology
  3. 3Departments of Oncology and Human Genetics, Program in Cancer Genetics, McGill University
Read full textPDFDOICite

Abstract

POLE or POLD1 deficiency (PPD) leads to an exceptionally high mutation burden and distinct mutational signatures that can inform immunotherapy responses. While some PPD-associated variants have been identified, many remain classified as variants of unknown significance. We analyzed 235,161 tumors across multiple datasets (GENIE, TCGA, and CPC) to develop a comprehensive catalog of PPD driver variants, using an iterative Support Vector Machine algorithm that incorporates both the number of SNVs and PPD-associated mutational signatures. Our iterative approach identified 581 PPD tumors and 65 driver variants, validating many previously reported variants and expanding this list. Thus, we curated the most comprehensive list of PPD drivers up to date. Notably, while the majority of POLE driver variants are located within the exonuclease domain (n = 39), we identified 3 new driver variants outside this domain. Additionally, 7.2% (n = 42) of the PPD samples did not harbor any driver variants, highlighting the need to classify tumors as PPD rather than relying solely on observed driver variants when making treatment decisions.

Related

  1. Proximity-mapped whole-genome sequencing for characterization of repeat expansions and variants in highly homologous genomic regions
    Y. Lin, L. Zhang, Y. Qiang +3
    medRxivPreprintAll rights reservedFull textHuman geneticsmedRxiv
  2. Comprehensive Molecular Profiling for Precision Diagnostics: Integrating Genomic, Proteomic, and Epigenetic Landscapes in Human Pathology
    Anandraj Vaithy K, Apoorv Shukla, Ajay Bhengra +3
    CureusPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. A comprehensive temporal proteome and phosphoproteome dataset of Y1 adrenocortical cells under FGF2 stimulation and SOS inhibition
    F. Montoni, T. Hanada, K. Doi +4
    bioRxivPreprintCC BYFull textOncologybioRxiv
  4. Comprehensive Genomic Profiling of Relapsed Interdigitating Dendritic Cell Sarcoma Reveals Novel Molecular Insights in a Patient Achieving Durable Remission After Autologous Stem Cell Transplantation
    Costantino Riemma, Chiara Cavatorta, Chiara Salvesi +10
    International Journal of Molecular SciencesPeer-reviewedCC BY 4.0General medicineCrossref
  5. Concealed right upper lobe pulmonary venous variants on 3D-CTBA: morphological characterization and surgical implications
    Luoyu Lian, Xin Luo, Dongliang Lin +3
    Frontiers in medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{dayan2026comprehensive,
  title = {{Comprehensive characterization of DNA polymerases driver variants using large genomic dataset}},
  author = {Dana Dayan and Hagay Ladany and Fabian Glaser and William D. Foulkes and Yosef E. Maruvka},
  journal = {Scientific Reports},
  year = {2026},
  month = aug,
  doi = {10.1038/s41598-026-62150-w},
  url = {https://doi.org/10.1038/s41598-026-62150-w},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Comprehensive characterization of DNA polymerases driver variants using large genomic dataset
AU  - Dana Dayan
AU  - Hagay Ladany
AU  - Fabian Glaser
AU  - William D. Foulkes
AU  - Yosef E. Maruvka
PY  - 2026
DA  - 2026/08/01
JO  - Scientific Reports
DO  - 10.1038/s41598-026-62150-w
UR  - https://doi.org/10.1038/s41598-026-62150-w
AB  - POLE or POLD1 deficiency (PPD) leads to an exceptionally high mutation burden and distinct mutational signatures that can inform immunotherapy responses. While some PPD-associated variants have been identified, many remain classified as variants of unknown significance. We analyzed 235,161 tumors across multiple datasets (GENIE, TCGA, and CPC) to develop a comprehensive catalog of PPD driver variants, using an iterative Support Vector Machine algorithm that incorporates both the number of SNVs and PPD-associated mutational signatures. Our iterative approach identified 581 PPD tumors and 65 driver variants, validating many previously reported variants and expanding this list. Thus, we curated the most comprehensive list of PPD drivers up to date. Notably, while the majority of POLE driver variants are located within the exonuclease domain (n = 39), we identified 3 new driver variants outside this domain. Additionally, 7.2% (n = 42) of the PPD samples did not harbor any driver variants, highlighting the need to classify tumors as PPD rather than relying solely on observed driver variants when making treatment decisions.
SN  - 2045-2322
ER  -