Frontiers in Genomics: Peter Van Loo
Molecular archeology of cancer

Resumen
Tumor development is driven by changes to the genome leading to fitness advantages underlying successive clonal expansions. As somatic changes occur across most or all cell cycles, the cancer genome carries an archeological record of its past. Over the past years, we have developed several approaches to mine that archeological record from the cancer genome, which we collectively call ‘molecular archeology of cancer’. Using these approaches, we are able to infer the subclonal architecture of tumors, and gain key insights into the order and timing of the genomic changes that occurred over their evolutionary history. We have applied these approaches in a large-scale pan-cancer setting, showing that intra-tumor heterogeneity is pervasive across cancers and that the timelines of tumor evolution span multiple years to decades. Key driver events in tumor evolution typically occur early, and copy number gains often accumulate as punctuated bursts, commonly after genome doubling. Late genome doubling is frequent in cancer evolution and is typically followed by an increase in the rate of copy number gains. Genome duplications affect the selection landscape of copy number losses, while only minimally impacting copy number gains. Extending our timing framework to time mutational signatures, we find that, as expected, environmentally associated mutations are associated with early tumor development. We also find evidence of episodic APOBEC mutagenesis across many tumors and clear timing patterns in many mutational processes that have unknown origins. Our approaches increase the evolutionary information that can be obtained from tumor genome sequences and, therefore, improve our understanding of the developmental history of cancer.

Peter Van Loo. Professor and CPRIT Scholar in Cancer Research. Department of Genetics. Department of Genomic Medicine. The University of Texas MD Anderson Cancer Center

https://www.mdanderson.org/research/departments-labs-institutes/labs/van-loo-laboratory.html

https://faculty.mdanderson.org/profiles/peter_vanloo.html

Frontiers in Genomics