Genomic and Transcriptomic Analyses of Malignant Pleural Mesothelioma (MPM) Samples Reveal Crucial Insights for Preclinical Testing
dc.contributor.author
Laure, Alexander
dc.contributor.author
Rigutto, Angelica
dc.contributor.author
Kirschner, Michaela B.
dc.contributor.author
Opitz, Lennart
dc.contributor.author
Grob, Linda
dc.contributor.author
Opitz, Isabelle
dc.contributor.author
Felley-Bosco, Emanuela
dc.contributor.author
Hiltbrunner, Stefanie
dc.contributor.author
Curioni-Fontecedro, Alessandra
dc.date.accessioned
2023-06-09T08:41:38Z
dc.date.available
2023-06-09T03:22:29Z
dc.date.available
2023-06-09T08:41:38Z
dc.date.issued
2023-05-02
dc.identifier.issn
2072-6694
dc.identifier.other
10.3390/cancers15102813
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/615780
dc.identifier.doi
10.3929/ethz-b-000615780
dc.description.abstract
Cell lines are extensively used to study cancer biology. However, the use of highly passaged commercial cell lines has to be questioned, as they do not closely resemble the originating tumor. To understand the reliability of preclinical models for Malignant pleural mesothelioma (MPM) studies, we have performed whole transcriptome and whole exome analyses of fresh frozen MPM tumors and compared them to cell lines generated from these tumors, as well as commercial cell lines and a preclinical MPM mouse model. Patient-derived cell lines were generated from digested fresh tumors and whole exome sequencing was performed on DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor samples, corresponding patient-derived cell lines, and normal tissue. RNA sequencing libraries were prepared from 10 fresh frozen tumor samples, the 10 corresponding patient-derived cell lines, and 7 commercial cell lines. Our results identified alterations in tumor suppressor genes such as FBXW7, CDKN2A, CDKN2B, and MTAP, all known to drive MPM tumorigenesis. Patient-derived cell lines correlate to a high degree with their originating tumor. Gene expressions involved in multiple pathways such as EMT, apoptosis, myogenesis, and angiogenesis are upregulated in tumor samples when compared to patient-derived cell lines; however, they are downregulated in commercial cell lines compared to patient-derived cell lines, indicating significant differences between the two model systems. Our results show that the genome and transcriptome of tumors correlate to a higher degree with patient-derived cell lines rather than commercial cell lines. These results are of major relevance for the scientific community in regard to using cell lines as an appropriate model, resembling the pathway of interest to avoid misleading results for clinical applications.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
MDPI
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
malignant pleural mesothelioma
en_US
dc.subject
patient-derived cell lines
en_US
dc.subject
preclinical models
en_US
dc.subject
transcriptomic analysis
en_US
dc.subject
genomic analysis
en_US
dc.title
Genomic and Transcriptomic Analyses of Malignant Pleural Mesothelioma (MPM) Samples Reveal Crucial Insights for Preclinical Testing
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2023-05-18
ethz.journal.title
Cancers
ethz.journal.volume
15
en_US
ethz.journal.issue
10
en_US
ethz.pages.start
2813
en_US
ethz.size
23 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Basel
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02892 - NEXUS Personalized Health Technologies / NEXUS Personalized Health Technologies
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02892 - NEXUS Personalized Health Technologies / NEXUS Personalized Health Technologies
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung / Domain VP Research::02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
ethz.date.deposited
2023-06-09T03:22:31Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2023-06-09T08:41:39Z
ethz.rosetta.lastUpdated
2024-02-02T23:59:37Z
ethz.rosetta.versionExported
true
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