Statistical Bioinformatics Webinar: Barbour -- Mutations in CTCF-cohesin Binding Sites in Cancer

Presented by Dr. Jayne Barbour (University of Hong Kong)

Mutations acquired in cancer genomes form distinct patterns. CTCF-cohesin binding sites
(CBS), or DNA loop anchors, and are vulnerable to accumulating mutations. To explore
why CBS are vulnerable to mutagenesis we performed analysis of somatic mutation
densities in CBS on 1980 whole-genome sequenced cancer samples. We found three groups
of samples with enriched CBS mutations densities: skin, gastrointestinal and XPD mutant
bladder cancers. XPD is a DNA helicase that is part of TFIIH and mutated in about 10%
of bladder cancer. XPD mutant samples displayed elevated mutation densities in
accessible chromatin and at transcriptionally active CBS. In a separate project, we
tested if a germline mutation in a specific CBS in the CDKN2B locus is important in
melanoma. Dermal fibroblasts from a family of sporadic melanoma harbouring this variant
were cultured and we performed CTCF ChIP-seq, HiC and RNA-seq. We observed
allele-specific loss of CTCF binding suggesting the variant is functional.