Human cell transformation by combined lineage conversion and oncogene expression

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dc.contributor.author Sahu, Biswajyoti
dc.contributor.author Pihlajamaa, Päivi
dc.contributor.author Zhang, Kaiyang
dc.contributor.author Palin, Kimmo
dc.contributor.author Ahonen, Saija
dc.contributor.author Cervera, Alejandra
dc.contributor.author Ristimäki, Ari
dc.contributor.author Aaltonen, Lauri A.
dc.contributor.author Hautaniemi, Sampsa
dc.contributor.author Taipale, Jussi
dc.date.accessioned 2021-09-16T07:45:01Z
dc.date.available 2021-09-16T07:45:01Z
dc.date.issued 2021-09-09
dc.identifier.citation Sahu , B , Pihlajamaa , P , Zhang , K , Palin , K , Ahonen , S , Cervera , A , Ristimäki , A , Aaltonen , L A , Hautaniemi , S & Taipale , J 2021 , ' Human cell transformation by combined lineage conversion and oncogene expression ' , Oncogene , vol. 40 , pp. 5533-5547 . https://doi.org/10.1038/s41388-021-01940-0
dc.identifier.other PURE: 168328393
dc.identifier.other PURE UUID: d94dafde-bb3b-4084-aa00-83bb4a6383a4
dc.identifier.other WOS: 000676064800002
dc.identifier.other ORCID: /0000-0001-6576-5440/work/100080565
dc.identifier.other ORCID: /0000-0002-7749-2694/work/100082556
dc.identifier.other ORCID: /0000-0003-3313-784X/work/100083280
dc.identifier.other ORCID: /0000-0001-6839-4286/work/101502619
dc.identifier.uri http://hdl.handle.net/10138/334405
dc.description.abstract Cancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Oncogene
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject HEPATOCELLULAR-CARCINOMA
dc.subject HUMAN FIBROBLASTS
dc.subject RAS ONCOGENES
dc.subject CANCER
dc.subject TUMOR
dc.subject GENES
dc.subject MYC
dc.subject METHYLATION
dc.subject INDUCTION
dc.subject TUMORIGENESIS
dc.subject 3122 Cancers
dc.title Human cell transformation by combined lineage conversion and oncogene expression en
dc.type Article
dc.contributor.organization Department of Biochemistry and Developmental Biology
dc.contributor.organization Digital Precision Cancer Medicine (iCAN)
dc.contributor.organization ATG - Applied Tumor Genomics
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Research Program in Systems Oncology
dc.contributor.organization Sampsa Hautaniemi / Principal Investigator
dc.contributor.organization Lauri Antti Aaltonen / Principal Investigator
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Research Programs Unit
dc.contributor.organization Department of Pathology
dc.contributor.organization HUSLAB
dc.contributor.organization Medicum
dc.contributor.organization HUS Diagnostic Center
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization Faculty Common Matters
dc.contributor.organization Bioinformatics
dc.contributor.organization Jussi Taipale / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41388-021-01940-0
dc.relation.issn 0950-9232
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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