A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues
- Author
- Tom Luijts (UGent) , Kerryn Elliott, Joachim Siaw (UGent) , Joris Van de Velde (UGent) , Elien Beyls (UGent) , Arne Claeys (UGent) , Tim Lammens (UGent) , Erik Larsson, Wouter Willaert (UGent) , Anne Vral (UGent) and Jimmy Van den Eynden (UGent)
- Organization
- Project
-
- Immunoediting and immune evasion mechanisms in the treated and untreated cancer genome
- Onderzoeksbeurs EvdS (Tom Luijts): Development of a multi-organ mutational clonality atlas to understand the foundation of human carcinogenesis
- Understanding tumour-immune interactions and cancer immunotherapy responses from differential immune selection pressures in the cancer genome
- Abstract
- Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumor evolution.
- Keywords
- Multidisciplinary, EXPANSION, SELECTION, CLONES, BCORL1
Downloads
-
Luijts Scientific Reports 2022.pdf
- full text (Published version)
- |
- open access
- |
- |
- 1.89 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8756936
- MLA
- Luijts, Tom, et al. “A Clinically Annotated Post-Mortem Approach to Study Multi-Organ Somatic Mutational Clonality in Normal Tissues.” SCIENTIFIC REPORTS, vol. 12, 2022, doi:10.1038/s41598-022-14240-8.
- APA
- Luijts, T., Elliott, K., Siaw, J., Van de Velde, J., Beyls, E., Claeys, A., … Van den Eynden, J. (2022). A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues. SCIENTIFIC REPORTS, 12. https://doi.org/10.1038/s41598-022-14240-8
- Chicago author-date
- Luijts, Tom, Kerryn Elliott, Joachim Siaw, Joris Van de Velde, Elien Beyls, Arne Claeys, Tim Lammens, et al. 2022. “A Clinically Annotated Post-Mortem Approach to Study Multi-Organ Somatic Mutational Clonality in Normal Tissues.” SCIENTIFIC REPORTS 12. https://doi.org/10.1038/s41598-022-14240-8.
- Chicago author-date (all authors)
- Luijts, Tom, Kerryn Elliott, Joachim Siaw, Joris Van de Velde, Elien Beyls, Arne Claeys, Tim Lammens, Erik Larsson, Wouter Willaert, Anne Vral, and Jimmy Van den Eynden. 2022. “A Clinically Annotated Post-Mortem Approach to Study Multi-Organ Somatic Mutational Clonality in Normal Tissues.” SCIENTIFIC REPORTS 12. doi:10.1038/s41598-022-14240-8.
- Vancouver
- 1.Luijts T, Elliott K, Siaw J, Van de Velde J, Beyls E, Claeys A, et al. A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues. SCIENTIFIC REPORTS. 2022;12.
- IEEE
- [1]T. Luijts et al., “A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues,” SCIENTIFIC REPORTS, vol. 12, 2022.
@article{8756936, abstract = {{Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumor evolution.}}, articleno = {{10322}}, author = {{Luijts, Tom and Elliott, Kerryn and Siaw, Joachim and Van de Velde, Joris and Beyls, Elien and Claeys, Arne and Lammens, Tim and Larsson, Erik and Willaert, Wouter and Vral, Anne and Van den Eynden, Jimmy}}, issn = {{2045-2322}}, journal = {{SCIENTIFIC REPORTS}}, keywords = {{Multidisciplinary,EXPANSION,SELECTION,CLONES,BCORL1}}, language = {{eng}}, pages = {{11}}, title = {{A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues}}, url = {{http://doi.org/10.1038/s41598-022-14240-8}}, volume = {{12}}, year = {{2022}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: