npj Precision Oncology (Apr 2025)

The tandem duplicator phenotype may be a novel targetable subgroup in pancreatic cancer

  • Abdul R. Farooq,
  • Amy X. Zhang,
  • Michelle Chan-Seng-Yue,
  • James T. Topham,
  • Grainne M. O’Kane,
  • Gun Ho Jang,
  • Sandra Fischer,
  • Anna Dodd,
  • Spring Holter,
  • Julie Wilson,
  • Robert C. Grant,
  • Kyaw Lwin Aung,
  • George Zogopoulos,
  • Elena Elimova,
  • Rebecca Prince,
  • Raymond Jang,
  • Malcolm Moore,
  • James Biagi,
  • Patricia Tang,
  • Rachel Goodwin,
  • Oliver F. Bathe,
  • Marco Marra,
  • Janessa Laskin,
  • Daniel J. Renouf,
  • David F. Schaeffer,
  • Joanna M. Karasinska,
  • Faiyaz Notta,
  • Steven Gallinger,
  • Jennifer J. Knox,
  • Erica S. Tsang

DOI
https://doi.org/10.1038/s41698-025-00888-8
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 10

Abstract

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Abstract Tandem duplicator phenotype (TDP) consists of distinct genomic rearrangements where tandem duplications are randomly distributed. In this study, we characterized the prevalence and outcomes of TDP in a large series of prospectively sequenced tumors from patients with pancreatic ductal adenocarcinomas (PDAC). Whole-genome sequencing (WGS) was performed in 530 PDAC cases from the PanCuRx Initiative, COMPASS and PanGen/POG trials in Canada. Of 530 cases, 52 were identified as TDP (9.8%; 13 resected, 39 advanced). Etiological subgroups of TDP included BRCA1 (n = 9), CCNE1 (n = 4), and unknown (n = 39). Presence of TDP was not prognostic in resected specimens (p = 0.77) compared with non-HRD and non-TDP cases, described as typicals. In advanced cases, when stratified for only classical subtype cases, platinum therapy was correlated with longer response in non-BRCA1 TDP vs. typicals (p = 0.0036). There was no difference in overall survival between TDP and typicals (p = 0.5).TDP represents a potential novel targetable subgroup for chemotherapy selection in PDAC.