CDK7

Overview

CDK7 is a cyclin-dependent kinase that functions both as a component of the CDK-activating kinase (CAK) complex, phosphorylating and activating other CDKs, and as a transcriptional kinase within the TFIIH complex, phosphorylating RNA Pol II to drive transcriptional initiation. CDK7 inhibitors (e.g., SY-5609, CT7001) are under clinical investigation as transcriptional cyclin-dependent kinase inhibitors. Focal copy number loss of CDK7 at chromosome 5 has been identified in anaplastic thyroid carcinoma.

Alterations observed in the corpus

  • Focal copy number loss at chromosome 5 in anaplastic thyroid carcinoma (ATC), identified as part of a comprehensive genomic and evolutionary landscape analysis PMID:38412093.

Cancer types (linked)

  • THAP: CDK7 focal CNA loss on chromosome 5 detected in ATC; ATC represents the most aggressive form of thyroid cancer and harbors a substantially higher burden of CNAs compared to well-differentiated thyroid cancers PMID:38412093.

Co-occurrence and mutual exclusivity

  • CDK7 loss co-occurs in the context of widespread chromosomal instability that distinguishes ATC from papillary thyroid carcinoma (PTC); the CNA subtype landscape in ATC includes multiple concurrent losses PMID:38412093.

Therapeutic relevance

  • CDK7 loss in ATC has not been directly therapeutically exploited, but CDK7 inhibitors are under investigation in other solid tumors; loss of CDK7 in ATC may paradoxically reduce sensitivity to CDK7 inhibitor-based strategies.

Open questions

  • The functional consequences of CDK7 focal loss in ATC vs. CDK7 inhibitor sensitivity in CDK7-intact ATC cases have not been addressed in the corpus.

Sources

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