A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer.

Inglebert, Marine; Dettwiler, Martina; Hahn, Kerstin; Letko, Anna; Drögemüller, Cord; Doench, John; Brown, Adam; Memari, Yasin; Davies, Helen R; Degasperi, Andrea; Nik-Zainal, Serena; Rottenberg, Sven (2022). A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer. Scientific Reports, 12(1), p. 18051. Nature Publishing Group 10.1038/s41598-022-21706-2

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Mammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts. We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (CMT), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors. We established the long-term culture of 24 organoid lines from 16 dogs, including organoids derived from normal mammary epithelium or benign lesions. CMT organoids recapitulated key morphological and immunohistological features of the primary tissue from which they were derived, including hormone receptor status. Furthermore, genetic characteristics (driver gene mutations, DNA copy number variations, and single-nucleotide variants) were conserved within tumor-organoid pairs. We show how CMT organoids are a suitable model for in vitro drug assays and can be used to investigate whether specific mutations predict therapy outcomes. Specifically, certain CMT subtypes, such as PIK3CA mutated, estrogen receptor-positive simple carcinomas, can be valuable in setting up a preclinical model highly relevant to human breast cancer research. In addition, we could genetically modify the CMT organoids and use them to perform pooled CRISPR/Cas9 screening, where library representation was accurately maintained. In summary, we present a robust 3D in vitro preclinical model that can be used in translational research, where organoids from normal, benign as well as malignant mammary tissues can be propagated from the same animal to study tumorigenesis.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Inglebert, Marine Hélène Fanny, Dettwiler, Martina Andrea, Hahn, Kerstin Caroline, Letko, Anna, Drögemüller, Cord, Rottenberg, Sven

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture
500 Science > 590 Animals (Zoology)

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Pubmed Import

Date Deposited:

31 Oct 2022 11:25

Last Modified:

27 Nov 2023 15:11

Publisher DOI:

10.1038/s41598-022-21706-2

PubMed ID:

36302863

BORIS DOI:

10.48350/174257

URI:

https://boris.unibe.ch/id/eprint/174257

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