IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60808-z.html
   My bibliography  Save this article

Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial

Author

Listed:
  • Jennifer J. Knox

    (University Health Network)

  • Gun Ho Jang

    (Ontario Institute for Cancer Research)

  • Robert C. Grant

    (University Health Network
    Ontario Institute for Cancer Research)

  • Amy Zhang

    (Ontario Institute for Cancer Research)

  • Lucy Ma

    (University Health Network)

  • Elena Elimova

    (University Health Network)

  • Raymond Jang

    (University Health Network)

  • Malcolm Moore

    (University Health Network)

  • James Biagi

    (Kingston Health Sciences Centre)

  • Mustapha Tehfe

    (Centre Hospitalier de l’Université de Montréal (CHUM))

  • Ravi Ramjeesingh

    (QEII Health Sciences Centre)

  • Erica S. Tsang

    (University Health Network)

  • Spring Holter

    (University Health Network)

  • Stephanie Ramotar

    (University Health Network)

  • Shawn Hutchinson

    (University Health Network)

  • Sheng-Ben Liang

    (University Health Network)

  • Ilinca M. Lungu

    (Ontario Institute for Cancer Research Toronto)

  • Shari Moura

    (University Health Network)

  • Yifan Wang

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Sheron Perera

    (University Health Network)

  • Michelle Chan-Seng-Yue

    (Ontario Institute for Cancer Research)

  • Maryam Monajemzadeh

    (University Health Network)

  • Kyaw Aung

    (The University of Texas at Austin)

  • Rebecca Prince

    (University Health Network)

  • Joan Miguel Romero

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Jesus Fuentes-Antras

    (University Health Network)

  • Galileo A. Gonzalez Conchas

    (University Health Network)

  • Sarah Picardo

    (University Health Network)

  • Ricardo Gonzalez

    (University Health Network)

  • Sangeet Ghai

    (University Health Network
    University of Toronto)

  • Korosh Khalili

    (University Health Network
    University of Toronto)

  • Tae Kyoung Kim

    (University Health Network
    University of Toronto)

  • Karen Ng

    (Ontario Institute for Cancer Research)

  • John Bartlett

    (University Health Network
    Western General Hospital)

  • Trevor J. Pugh

    (Ontario Institute for Cancer Research Toronto
    Princess Margaret Cancer Centre University Health Network)

  • Sangeetha N. Kalimuthu

    (University Health Network
    University Health Network)

  • Sandra E. Fischer

    (University Health Network
    University Health Network)

  • Julie M. Wilson

    (Ontario Institute for Cancer Research)

  • Anna Dodd

    (University Health Network)

  • George Zogopoulos

    (The Research Institute of the McGill University Health Centre
    The Rosalind & Morris Goodman Cancer Institute)

  • Barbara T. Grünwald

    (University Health Network
    University Hospital Essen
    West German Cancer Center)

  • Faiyaz Notta

    (University Health Network
    Ontario Institute for Cancer Research)

  • Steven Gallinger

    (University Health Network
    Ontario Institute for Cancer Research)

  • Grainne M. O’Kane

    (University Health Network
    University College Dublin)

Abstract

Integrated whole genome and transcriptome sequencing can unveil distinct molecular subgroups in pancreatic cancer (PDAC). The COMPASS trial (NCT02750657) enrolled 268 patients with advanced PDAC; patients were given either modified (m) FOLFIRINOX or Gemcitabine-nab-paclitaxel (GnP) as per physicians choice. Median follow-up is 52 months and median overall survival in those receiving mFOLFIRINOX is 10.6 months and 8.4 months for GnP. KRAS specific mutants and allelic states alone are not prognostic; however basal-like PDAC are more likely to harbour major imbalances in mutant KRAS (KRASmaj). In the presence of KRASmaj, pre-existing type II DM is more common. Distinct prognostic cohorts include homologous-recombination deficient PDAC, predictive of mFOLFIRINOX response. Basal-like PDAC and patients exhibiting evidence of systemic inflammation as annotated using the Gustave Roussy Immune Score are unique poor prognostic cohorts. The latter associates with low CD8 T cell infiltration while basal-like PDAC documents an inflamed tumour microenvironment.

Suggested Citation

  • Jennifer J. Knox & Gun Ho Jang & Robert C. Grant & Amy Zhang & Lucy Ma & Elena Elimova & Raymond Jang & Malcolm Moore & James Biagi & Mustapha Tehfe & Ravi Ramjeesingh & Erica S. Tsang & Spring Holter, 2025. "Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60808-z
    DOI: 10.1038/s41467-025-60808-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60808-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60808-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Faiyaz Notta & Michelle Chan-Seng-Yue & Mathieu Lemire & Yilong Li & Gavin W. Wilson & Ashton A. Connor & Robert E. Denroche & Sheng-Ben Liang & Andrew M. K. Brown & Jaeseung C. Kim & Tao Wang & Jared, 2016. "A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns," Nature, Nature, vol. 538(7625), pages 378-382, October.
    2. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Rotem Katzir & Noam Rudberg & Keren Yizhak, 2022. "Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    7. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Ewart Kuijk & Onno Kranenburg & Edwin Cuppen & Arne Van Hoeck, 2022. "Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    9. Sebastien Martinez & Shifei Wu & Michael Geuenich & Ahmad Malik & Ramona Weber & Tristan Woo & Amy Zhang & Gun Ho Jang & Dzana Dervovic & Khalid N. Al-Zahrani & Ricky Tsai & Nassima Fodil & Philippe G, 2024. "In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Yoonhee Nam & Karen Gomez & Jean-Baptiste Reynier & Cole Khamnei & Michael Aitken & Vivian Zheng & Tenzin Lhakhang & Milena Casula & Giuseppe Palmieri & Antonio Cossu & Arnold Levine & Enrico Tiacci &, 2025. "Genomic landscape of virus-associated cancers," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    11. Taichi Igarashi & Marianne Mazevet & Takaaki Yasuhara & Kimiyoshi Yano & Akifumi Mochizuki & Makoto Nishino & Tatsuya Yoshida & Yukihiro Yoshida & Nobuhiko Takamatsu & Akihide Yoshimi & Kouya Shiraish, 2023. "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    12. Sophie Pénisson & Amaury Lambert & Cristian Tomasetti, 2022. "Evaluating cancer etiology and risk with a mathematical model of tumor evolution," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Sujath Abbas & Oriol Pich & Ginny Devonshire & Shahriar A. Zamani & Annalise Katz-Summercorn & Sarah Killcoyne & Calvin Cheah & Barbara Nutzinger & Nicola Grehan & Nuria Lopez-Bigas & Rebecca C. Fitzg, 2023. "Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Chengdi Wang & Jingwei Li & Jingyao Chen & Zhoufeng Wang & Guonian Zhu & Lujia Song & Jiayang Wu & Changshu Li & Rong Qiu & Xuelan Chen & Li Zhang & Weimin Li, 2025. "Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    15. Noah Sasa & Toshihiro Kishikawa & Masashi Mori & Rie Ito & Yumie Mizoro & Masami Suzuki & Hirotaka Eguchi & Hidenori Tanaka & Takahito Fukusumi & Motoyuki Suzuki & Yukinori Takenaka & Keisuke Nimura &, 2025. "Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    16. Yuzhen Li & Ngoc K. Dang & Wei He & Mark Returan & Denisse Carvajal-Maldonado & Adele T. Guerin & Han Xu & Bin Liu & Richard D. Wood, 2025. "Pol θ-mediated end-joining uses microhomologies containing mismatches," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    17. Pierre Murat & Guillaume Guilbaud & Julian E. Sale, 2024. "DNA replication initiation drives focal mutagenesis and rearrangements in human cancers," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    18. Sriram Vijayraghavan & Thomas Blouin & James McCollum & Latarsha Porcher & François Virard & Jiri Zavadil & Carol Feghali-Bostwick & Natalie Saini, 2024. "Widespread mutagenesis and chromosomal instability shape somatic genomes in systemic sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Josefine Radke & Naveed Ishaque & Randi Koll & Zuguang Gu & Elisa Schumann & Lina Sieverling & Sebastian Uhrig & Daniel Hübschmann & Umut H. Toprak & Cristina López & Xavier Pastor Hostench & Simone B, 2022. "The genomic and transcriptional landscape of primary central nervous system lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    20. Tongwu Zhang & Jian Sang & Phuc H. Hoang & Wei Zhao & Jennifer Rosenbaum & Kofi Ennu Johnson & Leszek J. Klimczak & John McElderry & Alyssa Klein & Christopher Wirth & Erik N. Bergstrom & Marcos Díaz-, 2025. "APOBEC affects tumor evolution and age at onset of lung cancer in smokers," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60808-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.