TY - JOUR
T1 - Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues
T2 - an update of the Network of Cancer Genes (NCG) resource
AU - Dressler, Lisa
AU - Bortolomeazzi, Michele
AU - Keddar, Mohamed
AU - Misetic, Hrvoje
AU - Sartini, Giulia
AU - Acha-Sagredo, Amelia
AU - Montorsi, Lucia
AU - Wijewardhane, Neshika
AU - Repana, Dimitra
AU - Nulsen, Joel
AU - Goldman, Jacki
AU - Pollit, Marc
AU - Davis, Patrick
AU - Strange, Amy
AU - Ambrose, Karen
AU - Ciccarelli, Francesca
N1 - Funding Information:
This work was supported by the Cancer Research UK [C43634/A25487], the Cancer Research UK King’s Health Partners Centre at King’s College London [C604/A25135], the Cancer Research UK City of London Centre [C7893/A26233], the innovation programme under the Marie Skłodowska-Curie grant agreement [CONTRA-766030], the EPSRC Centre for Doctoral Training in Cross-Disciplinary Approaches to Non-Equilibrium Systems (CANES, EP/L015854/1), the Health Education England Genomics Education Programme, and the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001002), the UK Medical Research Council (FC001002), and the Wellcome Trust (FC001002). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.
Funding Information:
We thank Steve Hindmarsh and Stefan Boeing for their contribution to the development of the NCG database and website. Anahita Bishop and Barbara Cheifet were the primary editors of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. The review history is available as Additional?file?10.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/1/26
Y1 - 2022/1/26
N2 - BACKGROUND: Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development.RESULTS: Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation.CONCLUSIONS: Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/ .
AB - BACKGROUND: Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development.RESULTS: Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation.CONCLUSIONS: Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/ .
UR - http://www.scopus.com/inward/record.url?scp=85123588847&partnerID=8YFLogxK
U2 - 10.1186/s13059-022-02607-z
DO - 10.1186/s13059-022-02607-z
M3 - Article
C2 - 35078504
SN - 1474-760X
VL - 23
JO - Genome Biology
JF - Genome Biology
IS - 1
M1 - 35
ER -