Transcriptional analyses of acinar- and ductal-cell-derived pancreatic cancer
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Chu, Ken H.
issued: 2024-08-06T17:48:20Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, with one of the lowest 5-year survival rates at 10% across all cancers. In mouse models, PDAC arises from acinar or ductal cells, and previous transcriptomic analyses have identified specific markers of acinar- and ductal-cell-derived PDAC. However, although we have developed a more comprehensive understanding of the cellular origin of PDAC from mouse models, this knowledge has not been effectively utilized to classify patient tumors. Here, we generated mouse models where acinar or ductal cells, using Ptf1aCreER or Sox9CreER, respectively, expressed oncogenic Kras in the absence of Trp53 or Pten and formed PDAC tumors. Using both in vivo and in vitro methods, we reveal that acinar- and ductal-cell-derived tumors are largely similar to one another with small differences in gene expression. We also found variability in the expression levels of previously predicted markers of cellular origin and propose a more comprehensive set of transcriptomic markers. Moreover, our acinar-cell-derived PDAC samples showed enrichment in the classical subtype, consistent with previous studies, while basal subtype genes were expressed at similar levels across both cellular origins. Overall, our findings demonstrate that acinar and ductal tumors have similar expression profiles and require further research to elucidate the reliability of markers for diagnostic use.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88875
note: TRANSCRIPTIONAL ANALYSES OF ACINAR- AND DUCTAL-CELL-DERIVED PANCREATIC CANCER by Ken H. Chu B.Sc., The University of British Columbia, 2021 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Cell and Developmental Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2024 © Ken H. Chu, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis entitled: Transcriptional Analyses of Acinar- And Ductal-Cell-Derived Pancreatic Cancer. submitted by Ken H. Chu in partial fulfillment of the requirements for the degree of Master of Science in Cell and Developmental Biology Examining Committee: Dr. Janel Kopp, Cell and Developmental Biology, UBC Supervisor Dr. Michael Underhill, Cell and Developmental Biology, UBC Supervisory Committee Member Dr. Kevin Bennewith, Department of Pathology and Laboratory Medicine, UBC Supervisory Committee Member Dr. Catherine Van Raamsdonk, Department of Medical Genetics, UBC Additional Examiner iii Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, with one of the lowest 5-year survival rates at 10% across all cancers. In mouse models, PDAC arises from acinar or ductal cells, and previous transcriptomic analyses have identified specific markers of acinar- and ductal-cell-derived PDAC. However, although we have developed a more comprehensive understanding of the cellular origin of PDAC from mouse models, this knowledge has not been effectively utilized to classify patient tumors. Here, we generated mouse models where acinar or ductal cells, using Ptf1aCreER or Sox9CreER, respectively, expressed oncogenic Kras in the absence of Trp53 or Pten and formed PDAC tumors. Using both in vivo and in vitro methods, we reveal that acinar- and ductal-cell-derived tumors are largely similar to one another with small…
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0444995
language: eng
degree discipline: Cell and Developmental Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Kopp, Janel
type: Text
identifier URI: http://hdl.handle.net/2429/88875