The tandem duplicator phenotype may be a novel targetable subgroup in pancreatic cancer
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.
Authors
- Daniel J. Renouf (ORCID: https://orcid.org/0000-0002-7597-6089)
- Malcolm J. Moore (ORCID: https://orcid.org/0009-0007-7493-3558)
- Erica S. Tsang (ORCID: https://orcid.org/0000-0003-2317-2721)
- Rachel Goodwin (ORCID: https://orcid.org/0000-0002-0250-8479)
- Steven Gallinger (ORCID: https://orcid.org/0000-0002-6998-9414)
- Grainne M. O’Kane (ORCID: https://orcid.org/0000-0002-8690-403X)
- Abdul Rehman Farooq (ORCID: https://orcid.org/0000-0001-5433-6245)
- Patricia A. Tang (ORCID: https://orcid.org/0000-0003-1497-8539)
- James Biagi (ORCID: https://orcid.org/0000-0001-9233-7396)
- Michelle Chan‐Seng‐Yue (ORCID: https://orcid.org/0000-0003-3773-9354)
- Anna Dodd (ORCID: https://orcid.org/0000-0003-0649-0760)
- George Zogopoulos (ORCID: https://orcid.org/0000-0002-0482-7086)
- Joanna M. Karasinska (ORCID: https://orcid.org/0000-0001-6861-4189)
- Amy Xian Zhang (ORCID: https://orcid.org/0000-0001-9462-9835)
- Faiyaz Notta (ORCID: https://orcid.org/0000-0002-5748-3985)
- Rebecca M. Prince (ORCID: https://orcid.org/0000-0002-7989-6537)
- Oliver F. Bathe (ORCID: https://orcid.org/0000-0003-2305-4602)
- Jennifer J. Knox (ORCID: https://orcid.org/0000-0003-3474-6647)
- Marco A. Marra (ORCID: https://orcid.org/0000-0001-7146-7175)
- Julie M. Wilson (ORCID: https://orcid.org/0000-0003-2510-962X)
- Sandra Elisabeth Fischer (ORCID: https://orcid.org/0000-0001-8859-4525)
- James T. Topham (ORCID: https://orcid.org/0009-0001-6601-8807)
- Robert C. Grant (ORCID: https://orcid.org/0000-0002-9821-0377)
- Janessa Laskin (ORCID: https://orcid.org/0000-0002-0161-9329)
- Gun Ho Jang (ORCID: https://orcid.org/0000-0001-8169-7011)
- Spring Holter
- David F. Schaeffer (ORCID: https://orcid.org/0000-0002-7341-1308)
- Kyaw Aung (ORCID: https://orcid.org/0000-0003-2910-2847)
- Raymond Jang
- Elena Elimova
Institutions
- Ontario Institute for Cancer Research (CA)
- University of British Columbia (CA)
- University of Ottawa (CA)
- University of Calgary (CA)
- University of Toronto (CA)
- Queen's University (CA)
- Ottawa Hospital (CA)
- McGill University Health Centre (CA)
- Princess Margaret Cancer Centre (CA)
- Vancouver General Hospital (CA)
- St. James's Hospital (IE)
- The University of Texas at Austin (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1038/s41698-025-00888-8
- Citations
- 1
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- Princess Margaret Cancer Foundation
- Ontario Institute for Cancer Research
- Government of Ontario
- Terry Fox Research Institute
- Canadian Cancer Society Research Institute