Ahrenfeldt, J.; Christensen, D.S.; Sokač, M.; Kisistók, J.; McGranahan, N.; Birkbak, N.J. Computational Analysis Reveals the Temporal Acquisition of Pathway Alterations during the Evolution of Cancer. Cancers2022, 14, 5817.
Ahrenfeldt, J.; Christensen, D.S.; Sokač, M.; Kisistók, J.; McGranahan, N.; Birkbak, N.J. Computational Analysis Reveals the Temporal Acquisition of Pathway Alterations during the Evolution of Cancer. Cancers 2022, 14, 5817.
Ahrenfeldt, J.; Christensen, D.S.; Sokač, M.; Kisistók, J.; McGranahan, N.; Birkbak, N.J. Computational Analysis Reveals the Temporal Acquisition of Pathway Alterations during the Evolution of Cancer. Cancers2022, 14, 5817.
Ahrenfeldt, J.; Christensen, D.S.; Sokač, M.; Kisistók, J.; McGranahan, N.; Birkbak, N.J. Computational Analysis Reveals the Temporal Acquisition of Pathway Alterations during the Evolution of Cancer. Cancers 2022, 14, 5817.
Abstract
: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.
Keywords
metastasis; cancer evolution; bioinformatics; cancer biology; cancer genomics
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
