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A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues

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) , et al.
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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

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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}},
}

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