Transformed Canine and Murine Mesenchymal Stem Cells as a Model for Sarcoma with Complex Genomics.

complex genomics mesenchymal stem cells osteosarcoma sarcoma undifferentiated pleomorphic sarcoma undifferentiated sarcoma

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
05 Mar 2021
Historique:
received: 27 01 2021
revised: 23 02 2021
accepted: 28 02 2021
entrez: 3 4 2021
pubmed: 4 4 2021
medline: 4 4 2021
Statut: epublish

Résumé

Sarcomas are rare mesenchymal tumors with a broad histological spectrum, but they can be divided into two groups based on molecular pathology: sarcomas with simple or complex genomics. Tumors with complex genomics can have aneuploidy and copy number gains and losses, which hampers the detection of early, initiating events in tumorigenesis. Often, no benign precursors are known, which is why good models are essential. The mesenchymal stem cell (MSC) is the presumed cell of origin of sarcoma. In this study, MSCs of murine and canine origin are used as a model to identify driver events for sarcomas with complex genomic alterations as they transform spontaneously after long-term culture. All transformed murine but not canine MSCs formed sarcomas after subcutaneous injection in mice. Using whole genome sequencing, spontaneously transformed murine and canine MSCs displayed a complex karyotype with aneuploidy, point mutations, structural variants, inter-chromosomal translocations, and copy number gains and losses. Cross-species analysis revealed that point mutations in

Identifiants

pubmed: 33807947
pii: cancers13051126
doi: 10.3390/cancers13051126
pmc: PMC7961539
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Netherlands Organization for Scientific Research
ID : ZON-MW VICI 170.055

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Auteurs

Natasja Franceschini (N)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Bas Verbruggen (B)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Marianna A Tryfonidou (MA)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.

Alwine B Kruisselbrink (AB)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Hans Baelde (H)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Karin E de Visser (KE)

Division of Tumour Biology & Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Oncode Institute, Office Jaarbeurs Innovation Mile (JIM), Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands.

Karoly Szuhai (K)

Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Anne-Marie Cleton-Jansen (AM)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Judith V M G Bovée (JVMG)

Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Classifications MeSH