期刊
GENOME BIOLOGY
卷 23, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13059-022-02607-z
关键词
Driver genes; Somatic evolution; Cancer initiation; Systems-level properties
资金
- Cancer Research UK [C43634/A25487]
- Cancer Research UK King's Health Partners Centre at King's College London [C604/A25135]
- Cancer Research UK City of London Centre [C7893/A26233]
- innovation programme under the Marie Sklodowska-Curie grant agreement [CONTRA-766030]
- EPSRC Centre for Doctoral Training in Cross-Disciplinary Approaches to Non-Equilibrium Systems (CANES) [EP/L015854/1]
- Health Education England Genomics Education Programme
- Francis Crick Institute from Cancer Research UK [FC001002]
- UK Medical Research Council [FC001002]
- Wellcome Trust [FC001002]
This study compiled 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. The analysis of these genes revealed that the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. There is a high overlap between drivers of cancer and non-cancer somatic evolution, although significant differences exist in their recurrence. Additionally, a set of evolutionarily conserved and essential genes were identified, and alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation.
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/.
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