CDKN2B

Overview

CDKN2B encodes p15^INK4b, a cyclin-dependent kinase inhibitor co-located with CDKN2A on 9p21 and typically co-deleted, contributing to cell-cycle dysregulation.

Alterations observed in the corpus

  • CDKN2A/CDKN2B alterations were more frequent in NSCLC brain metastases (34%) than in primary tumors (13%; p=0.003, q=0.04); cell-cycle pathway alterations were 56% in BM vs 32% in PT (p=0.004, q=0.041), with the pathway enrichment driven by CDKN2A/B PMID:37591896.
  • In the LUAD sub-cohort the CDKN2A/B enrichment persisted (31% BM vs 18% PT; p=0.004) PMID:37591896.
  • Frequently co-altered with FGFR3 in urothelial carcinoma (alongside CDKN2A and KDM6A) in the MSK bladder_msk_2023 cohort PMID:37682528.
  • Homozygous CDKN2A/B deletion defined “molecular grade-high” in IDH-mutant low-grade glioma and drove ~2x faster tumor volume growth rate (19.17% vs 9.54% per 6 months) during active surveillance PMID:37910594.
  • CDKN2A/CDKN2B co-deletions were nearly universal in RT-MPNST (92% vs 44% sporadic), present in 29% of RT-MFH (UPS) and 33% of RT-OS, but almost absent in RT-ANGS (2%) in a comparative genomic analysis of 82 radiation-associated sarcomas PMID:37350195.
  • CDKN2A/CDKN2B alterations associated with inferior PFS on multivariable analysis in metastatic esophagogastric cancer treated with pembrolizumab + trastuzumab + chemotherapy PMID:37406106.
  • Homozygous CDKN2A/CDKN2B deletions and loss-of-function in 28% of FP-RMS; correlated with worse OS (p=0.049) and PFS (p=0.0082) PMID:37730754.
  • Classical DPM driver; not enriched in the genomic near-haploidization (GNH) subset of diffuse pleural mesothelioma PMID:38630790.
  • Loss acquired in a recurrent, metastatic pituitary neuroendocrine tumor (patient TR-9) together with CCND3 amplification PMID:38758238.
  • Deletions co-occurring with BRAF fusions in 12% of BRAF fusion-positive tumors across histologies PMID:38922339.
  • In 2,336 PDAC patients (pdac_msk_2024), CDKN2A/CDKN2B alteration rate increased from 44% (resectable) to 60% (metastatic) (P = 6.9 × 10⁻⁵), establishing stage-dependent CDKN2B loss as a prognostic marker of PDAC progression PMID:39753968.
  • Homozygous deletion of the CDKN2A/CDKN2B locus is extremely common (over 50%) in GBM; part of the RB pathway (52% altered) PMID:18772890.
  • Frequently deleted alongside CDKN2A in LUAD (TSP, n=188); cell cycle tumour suppressor in CDK4/6-cyclin D pathway. PMID:18948947
  • CDKN2B deletions in 14% of GBC; frequently co-deleted with CDKN2A PMID:36228155
  • Homozygous deletions identified as rare but potentially significant events; frequently co-occurring with CDKN2A and MTAP loss in the METABRIC breast cancer cohort (2,000 tumors) PMID:22522925
  • Deleted in ALL (St. Jude WGS/WES, 44 tumors); CDKN2B deletion co-occurs with CDKN2A deletion in pediatric acute lymphoblastic leukemia, compounding loss of cell-cycle inhibition PMID:23334668
  • 9p21.3 homozygous deletion co-occurring with CDKN2A deletion in high-grade bladder tumors PMID:23897969
  • Homozygous focal deletion at 9p21 in 50/99 (50%) of bladder TCC tumors, co-deleted with CDKN2A PMID:24121792
  • Homozygous deletion together with CDKN2A in PanNEN patient PN16; supported CDK4/6-inhibitor therapy recommendation in WGTA-guided therapy study PMID:24326773
  • Deletion/mutation in 15–27% of intrahepatic CCA and 19% of extrahepatic CCA (co-deleted with CDKN2A); deletion emergence as an acquired-resistance mechanism in FGFR2 fusion-positive iCCA after FGFR inhibitor therapy PMID:25526346
  • 9p21 deletion peak co-affected with CDKN2A in cutaneous squamous cell carcinoma (29-tumor cSCC NGS cohort) PMID:25589618
  • Frequently deleted in PDAC (36% in pathway analysis); dominant RB-pathway lesion co-occurring with CDK4/CCND1 amplification PMID:25855536
  • 9p21.3 deletion in 83% of PCNSL (homozygous in 55%), co-deleted with CDKN2A PMID:25991819
  • Cell-cycle pathway aberration in mCRPC; potential CDK4 inhibitor candidate PMID:26000489
  • Alterations evenly distributed across BRAF/RAS/NF1 melanoma subtypes PMID:26091043
  • Homozygous deletions enriched in high-grade UTUC vs high-grade UCB (15.3% vs 3.9%, p=0.016); one of the most significantly differentially altered genes between UTUC and bladder cancer PMID:26278805
  • Homozygous loss co-occurred with CDKN2A loss in the recurrent medulloblastoma clone of patient MB-REC-12 after therapy-mediated elimination of the PTCH1-driven primary clone PMID:26760213
  • Mentioned in study PMID:26824661
  • 9p21 codeletion (with CDKN2A and MTAP) defines CN Cluster A in urothelial carcinoma; co-deleted with CDKN2A as tumor progressed from heterozygous to homozygous deletion in post-chemotherapy metastases PMID:27749842
  • Deletion in 2/19 sequenced anaplastic oligodendroglioma tumors; co-deleted with CDKN2A and PTEN in a false-positive 1p/19q FISH case with glioblastoma-like signature (odg_msk_2017) PMID:28472509

Cancer types (linked)

  • NSCLC brain metastasis — CDKN2B deep deletion, co-occurring with CDKN2A, marks cell-cycle pathway dysregulation as a near-obligate event for BM development PMID:37591896.
  • MPNST — CDKN2A/B co-deletions in 92% of RT-MPNST (vs 44% sporadic), the most enriched alteration in RT-MPNST PMID:37350195.
  • MFH (UPS) — CDKN2A/B co-deletions in 29% of RT-UPS PMID:37350195.
  • OS — CDKN2A/B co-deletions in 33% of RT-OS PMID:37350195.
  • ANGS — CDKN2A/B co-deletions rare (2%) in RT-AS, distinguishing it from other RT-sarcoma histotypes PMID:37350195.
  • PAAD — CDKN2A/CDKN2B alteration rate climbs with stage (44% resectable → 60% metastatic, P = 6.9 × 10⁻⁵) in the 2,336-patient pdac_msk_2024 cohort PMID:39753968.
  • EGC (EGC/STAD) — CDKN2A/CDKN2B alterations associated with inferior PFS in the HER2+/PD-1 blockade setting PMID:37406106.
  • RMS/ARMS — homozygous deletions in 28% of FP-RMS; correlated with worse OS and PFS PMID:37730754.
  • PLMESO — classical DPM driver; not enriched in GNH mesothelioma subset PMID:38630790.
  • PTAD — loss acquired at recurrence in aggressive pituitary neuroendocrine tumor PMID:38758238.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • CDKN2A/B loss is proposed as a rationale for CDK4/6-directed strategies in CNS-tropic NSCLC, though not tested in the corpus PMID:37591896.

Open questions

  • Whether CDK4/6 inhibition modifies BM risk or outcome in CDKN2A/B-deleted NSCLC remains untested PMID:37591896.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26278805

This page was processed by crosslinker on 2026-05-14. - PMID:26760213

This page was processed by crosslinker on 2026-05-14. - PMID:26824661

This page was processed by wiki-cli on 2026-05-14. - PMID:27749842

This page was processed by entity-page-writer on 2026-05-15. - PMID:28472509

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