Publication: non-coding cancer drivers validated in Cell Reports
“Functional identification of non-coding regulatory regions that drive breast and skin carcinogenesis” is published in Cell Reports. The study is a collaboration with Daniel Schramek’s lab at the Lunenfeld-Tanenbaum Research Institute that combines computational cancer genomics with extensive experimental validation of non-coding cancer drivers.
About 98% of the human genome is non-coding, including regulatory elements that control gene expression. Most cancer mutations fall in these regions, but telling genuine drivers apart from passenger mutations there is a major challenge. Using our ActiveDriverWGS method, we screened more than 300,000 regulatory elements across thousands of whole cancer genomes to find candidate non-coding drivers. Robin Oh, Daniel Schramek and team then tested these predictions with CRISPR screens in human cells and in vivo models of breast and skin cancer. Key findings:
- 12 non-coding regulatory elements can drive tumour formation.
- The driver mechanisms involve the oncogenic microRNA miR-21 and ZFP36L2, a p53-regulated tumour suppressor.
Robin Oh and Kevin Cheng (Reimand lab) are co-first authors, with Daniel Schramek and Jüri Reimand as co-corresponding authors. Congratulations to everyone involved, and thank you to CIHR for funding.