Over 65 posters were presented at the virtual EMBL Conference ‘Cancer genomics’, covering cancer genome projects, cancer functional genomics, systems biology, cancer immunogenomics and epigenomics, cancer mouse models and the translation and clinical impact of obtained scientific results. We are pleased to be able to share with you the research from the winner of the best poster prize, a €200 voucher sponsored by Molecular Oncology.

Characterization of mutational hotspots across cancer genomes

Presenter: Claudia Arnedo-Pac

Abstract

Thanks to the advent of whole genome sequencing into cancer research, the landscape to explore cancer drivers and the mutational processes generating somatic mutations has expanded. As a consequence, it has become clear that these analyses are tightly linked. A paradigmatic case of this is found in the interpretation of the recurrency of somatic mutations in the same nucleotide (hotspot), which can either be a signal of positive selection or a localized mutational process that does not provide selective advantage to the cells. To the best of our knowledge, a comprehensive characterization of mutational hotspots focusing on both coding and non-coding genomic regions is missing. In the present work, we aim to characterize the distribution of hotspots of somatic mutations to study the mutational processes that play a role in their formation and improve the prioritization of non-coding driver hotspots. With this objective, we have developed a new method, HotspotFinder, to identify, filter, and annotate hotspots of somatic single nucleotide variants (SNVs), multiple nucleotide variants (MNVs) and short indels across the genome. We have run HotspotFinder over 7,553 whole genomes from 81 publicly available cancer cohorts comprising 37 different cancer types. We have identified more than 700,000 hotspots pan-cancer. Across cancer types, we observe large variability in the number and mutation type of hotspots: cutaneous melanomas show the highest hotspot rate with the majority of hotspots arising from SNVs. On the contrary, most hotspots in colorectal cancers, non-small cell lung cancers, and breast cancers arise from insertions and deletions. These differences point to the diversity of mutational processes acting on cancer genomes. Ongoing analyses are focused on characterizing the contribution of different mutational signatures and genome covariates to the formation of hotspots across cancers. Finally, we are working towards prioritizing new candidate driver hotspots in non-coding regions.

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