CDKN1B

Overview

CDKN1B encodes p27 (KIP1), a cyclin-dependent kinase inhibitor that restrains cell cycle progression at G1 by binding and inhibiting cyclin E–CDK2 and cyclin A–CDK2 complexes. Loss of p27 function promotes unchecked proliferation and is a recognized mechanism of tumor progression, particularly in prostate cancer where it correlates with worse prognosis.

Alterations observed in the corpus

  • Identified as somatically altered in integrative genomic profiling of prostate cancer (MSKCC cohort) PMID:20579941
  • Somatic substitutions in 3/112 samples and deletions in 16; first report of somatic point mutations in this cell cycle regulator in prostate cancer; activated by FOXA1 PMID:22610119
  • CDKN1B mutations identified in breast cancer WES of 100 tumors, implicating cell cycle checkpoint loss in breast tumorigenesis PMID:22722201
  • Intermediate-clonality deletion in prostate carcinoma; recurrently disrupted in 3 cases via chromoplexy; co-deleted with ETV6/ETV3 in one 25-rearrangement chromoplexy chain PMID:23622249
  • Mutated as part of the significantly mutated cell-cycle gene set in multiple myeloma (MM, n=203); part of a 612-gene MSigDB scan that flagged cell-cycle genes as significantly mutated in this cohort PMID:24434212
  • Cell-cycle pathway aberration (RB1/CDKN2A/CDKN2B/CDK4 co-context) in mCRPC; potential CDK4 inhibitor candidate PMID:26000489
  • Significantly mutated gene in primary prostate cancer (TCGA prostate cohort); part of the recurrently mutated gene set MED12/CDKN1B/NKX3-1/ZMYM3 PMID:26544944
  • 12p13.1 heterozygous deletion in 5/25 (20%) Sézary syndrome cases PMID:26551667
  • Single-case CDKN1B mutation detected in PDTC/ATC thyroid cancer sequencing cohort (341-gene IMPACT panel, 117 tumors), replicating findings from prior WES ATC study PMID:26878173
  • CDKN1B was identified as a cell-cycle Mut-driver in breast cancer, listed among the 40 Mut-driver genes spanning Akt-signaling, cell-cycle, chromatin function, DNA damage, and apoptosis pathways PMID:27161491.
  • Identified as a novel recurrently mutated gene (1–4% frequency) in microsatellite-stable metastatic colorectal cancer by MSK-IMPACT sequencing of 1,134 colorectal adenocarcinomas PMID:29316426

Cancer types (linked)

  • PRAD: Somatic alteration detected in the MSKCC prostate cancer cohort as part of comprehensive genomic characterization PMID:20579941

Co-occurrence and mutual exclusivity

  • In prostate cancer, CDKN1B loss may co-occur with PTEN deletion and AR pathway alterations; specific co-mutation patterns in the corpus not yet characterized.

Therapeutic relevance

  • CDK4/6 inhibitors may partially compensate for CDKN1B loss; direct therapeutic targeting of p27 restoration remains investigational.

Open questions

  • Frequency and specific alteration type (deletion vs mutation) of CDKN1B in the MSKCC prostate cohort requires further detail from the source paper.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by wiki-cli on 2026-05-14. - PMID:26551667

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27161491

This page was processed by wiki-cli on 2026-05-14. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15.