A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues
Luijts, Tom ; Elliott, Kerryn ; Siaw, Joachim Tetteh LU
; Van de Velde, Joris
; Beyls, Elien
; Claeys, Arne
; Lammens, Tim
; Larsson, Erik
; Willaert, Wouter
and Vral, Anne
, et al.
(2022)
In Scientific Reports
12(1).
- 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... (More)
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.
(Less)
- author
- Luijts, Tom
; Elliott, Kerryn
; Siaw, Joachim Tetteh
LU
; Van de Velde, Joris
; Beyls, Elien
; Claeys, Arne
; Lammens, Tim
; Larsson, Erik
; Willaert, Wouter
and Vral, Anne
, et al. (More)
- Luijts, Tom
; Elliott, Kerryn
; Siaw, Joachim Tetteh
LU
; Van de Velde, Joris
; Beyls, Elien
; Claeys, Arne
; Lammens, Tim
; Larsson, Erik
; Willaert, Wouter
; Vral, Anne
and Van den Eynden, Jimmy
(Less)
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- in
- Scientific Reports
- volume
- 12
- issue
- 1
- article number
- 10322
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85132261365
- pmid:35725896
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-022-14240-8
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2022, The Author(s).
- id
- 540e6f68-f5e8-485d-8383-4ae75cc6deb0
- date added to LUP
- 2025-03-19 11:46:35
- date last changed
- 2025-06-25 20:06:30
@article{540e6f68-f5e8-485d-8383-4ae75cc6deb0,
abstract = {{<p>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.</p>}},
author = {{Luijts, Tom and Elliott, Kerryn and Siaw, Joachim Tetteh 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}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues}},
url = {{http://dx.doi.org/10.1038/s41598-022-14240-8}},
doi = {{10.1038/s41598-022-14240-8}},
volume = {{12}},
year = {{2022}},
}