DR-393 Distinctive size classes of loss of heterozygosity and homozygous deletion and its association with cancer progression and DNA repair pathways

Previous work from our institute has been published on analysis of WGS data that were made accessible by the Hartwig foundation (The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact. Lisanne F van Dessel et al. Nat Commun. 2019). In further work, we analyzed the number and size of deletions and homozygous deletions (HDs) in metastatic castration-resistant lesions and compared this to WGS data from localized prostate cancer (available from PCAWG and TCGA). The data suggested 4 distinctive size classes in deletions and homozygous deletions. Small and very small deletions were frequent in prostate cancer metastases but very rare in localized disease. There is a strong correlation between HD in BRCA2 and the presence of  small and very small deletions. We intend to further explore this observation by analyzing deletions, HDs, mutations and expression data of genes  involved in DNA repair pathways (both homologous recombination and non-homologous end joining pathways). Further, we want to investigate this in other tumor types such as breast and colon cancer.

Paul Verhagen, Erasmus MC, the Netherlands