Cancers with mutations in CDK12
The CDK12 gene is a cyclin-dependent kinase and controls the cell cycle, cell division, and transcription. 1 Cancers with pathogenic CDK12 mutations display chromosomal instability and their genomes are dominated by somatic tandem duplications.2 The mechanistic connection between the CDK12 loss and chromosomal instability remains unresolved, and uncovering the mechanism might inform new cancer therapies.
In order to explore the patterns of structural variants in cancers with CDK12 loss, we queried the PCAWG cancer genome dataset and created a Chromoscope configuration with 12 cancers with mutations in CDK12 likely to result in the loss of function.
The 12 cancer genomes are dominated by large (>100kb) duplications, with the burden of structural variants higher than the CCNE1 group. This visualization also features novel and compound patterns of structural variants (example).
You view the 12 cancer genomes with putative CDK12 loss-of-function at:
- Liu, Hui et al. “Targeting CDK12 for Cancer Therapy: Function, Mechanism, and Drug Discovery.” Cancer research vol. 81,1 (2021): 18-26. doi:10.1158/0008-5472.CAN-20-2245↩
- Menghi, Francesca et al. “The Tandem Duplicator Phenotype Is a Prevalent Genome-Wide Cancer Configuration Driven by Distinct Gene Mutations.” Cancer cell vol. 34,2 (2018): 197-210.e5. doi:10.1016/j.ccell.2018.06.008↩