Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma

James T. Topham, Erica S. Tsang, Joanna M. Karasinska, Andrew Metcalfe, Hassan Ali, Steve E. Kalloger, Veronika Csizmok, Laura M. Williamson, Emma Titmuss, Karina Nielsen, Gian Luca Negri, Sandra E. Spencer Miko, Gun Ho Jang, Robert E. Denroche, Hui-li Wong, Grainne M. O’Kane, Richard A. Moore, Andrew J. Mungall, Jonathan M. Loree, Faiyaz Notta, Julie M. Wilson, Oliver F. Bathe, Patricia A. Tang, Rachel Goodwin, Gregg B. Morin, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J. M. Jones, David F. Schaeffer and Daniel J. Renouf ()
Additional contact information
James T. Topham: Pancreas Centre BC
Erica S. Tsang: BC Cancer
Joanna M. Karasinska: Pancreas Centre BC
Andrew Metcalfe: Pancreas Centre BC
Hassan Ali: Pancreas Centre BC
Steve E. Kalloger: Pancreas Centre BC
Veronika Csizmok: BC Cancer
Laura M. Williamson: BC Cancer
Emma Titmuss: BC Cancer
Karina Nielsen: BC Cancer
Gian Luca Negri: BC Cancer
Sandra E. Spencer Miko: BC Cancer
Gun Ho Jang: Ontario Institute for Cancer Research
Robert E. Denroche: Ontario Institute for Cancer Research
Hui-li Wong: BC Cancer
Grainne M. O’Kane: Ontario Institute for Cancer Research
Richard A. Moore: BC Cancer
Andrew J. Mungall: BC Cancer
Jonathan M. Loree: BC Cancer
Faiyaz Notta: Ontario Institute for Cancer Research
Julie M. Wilson: Ontario Institute for Cancer Research
Oliver F. Bathe: University of Calgary
Patricia A. Tang: University of Calgary
Rachel Goodwin: Ottawa Hospital Research Institute
Gregg B. Morin: BC Cancer
Jennifer J. Knox: University of Toronto
Steven Gallinger: Ontario Institute for Cancer Research
Janessa Laskin: BC Cancer
Marco A. Marra: BC Cancer
Steven J. M. Jones: BC Cancer
David F. Schaeffer: Pancreas Centre BC
Daniel J. Renouf: Pancreas Centre BC

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33718-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33718-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33718-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().