Systematic Characterization of Recurrent Genomic Alterations in Cyclin-Dependent Kinases Reveals Potential Therapeutic Strategies for Cancer Treatment.

ABSTRACT: Recurrent copy-number alterations, mutations, and transcript fusions of the genes encoding CDKs/cyclins are characterized in >10,000 tumors. Genomic alterations of CDKs/cyclins are dominantly driven by copy number aberrations. In contrast to cell-cycle-related CDKs/cyclins, which are globally amplified, transcriptional CDKs/cyclins recurrently lose copy numbers across cancers. Although mutations and transcript fusions are relatively rare events, CDK12 exhibits recurrent mutations in multiple cancers. Among the transcriptional CDKs, CDK7 and CDK12 show the most significant copy number loss and mutation, respectively. Their genomic alterations are correlated with increased sensitivities to DNA-damaging drugs. Inhibition of CDK7 preferentially represses the expression of genes in the DNA-dama

SUBMITTER: Shan W 

PROVIDER: S-EPMC7391471 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature