CCND3

Overview

CCND3 encodes Cyclin D3, a member of the D-type cyclin family that promotes cell cycle G1-to-S transition by activating CDK4/6. CCND3 amplification has been observed as an acquired alteration in recurrent pituitary neuroendocrine tumors, where it may cooperate with CDKN2A/CDKN2B loss to drive aggressive, treatment-refractory behavior.

Alterations observed in the corpus

  • Amplification acquired in a recurrent, treatment-refractory pituitary neuroendocrine tumor (patient TR-9), co-occurring with CDKN2A/CDKN2B loss and genome-wide loss of heterozygosity PMID:38758238.
  • Expressed preferentially in differentiated (non-stem) tumor cells of grade II oligodendroglioma (IDH-mutant, 1p19q-codeleted); cyclin switching from CCND2 (stem/progenitor) to CCND1/CCND3 (differentiated) observed across 4,347 single cells from 6 tumors PMID:27806376.
  • Identified as recurrently mutated in DLBCL and FL by whole-genome/exome sequencing of non-Hodgkin lymphomas PMID:21796119
  • Identified as a recurrently mutated gene in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing of 55 tumors PMID:22343534
  • Identified as an additional significantly mutated gene (SMG) at <=8% frequency in muscle-invasive bladder carcinoma (BLCA, n=131); TCGA bladder urothelial carcinoma study PMID:24476821
  • Recurrent focal amplification in LUAD; identified as one of multiple significant amplification peaks in the TCGA lung adenocarcinoma dataset (n=230) PMID:25079552
  • CCND3 was identified as a novel focal amplification target in lung adenocarcinoma (Pan-Lung analysis) PMID:27158780.
  • CCND3 amplification listed as actionable alteration in cisplatin-resistant germ cell tumors, nominating CDK4/6 inhibitors PMID:27646943

Cancer types (linked)

  • PTAD: CCND3 amplification was observed as a secondary somatic event at recurrence in an aggressive pituitary neuroendocrine tumor with high fraction of LOH; may contribute to CDK4/6-driven cell cycle dysregulation PMID:38758238.
  • ODG — CCND3 marks the differentiated compartment of oligodendroglioma in a cyclin-switching model where CCND2 predominates in stem/progenitor cells PMID:27806376.

Co-occurrence and mutual exclusivity

  • Co-occurred with CDKN2A/CDKN2B loss in the same recurrent tumor, suggesting convergent cell cycle pathway activation (accelerator + brake) PMID:38758238.

Therapeutic relevance

  • The combination of CCND3 amplification and CDKN2A/CDKN2B loss in a recurrent tumor could rationale CDK4/6 inhibitor therapy in aggressive PitNETs, though no clinical data exist for this setting PMID:38758238.

Open questions

  • CCND3 amplification was observed in a single recurrent case; its prevalence and prognostic significance across PitNET cohorts require systematic evaluation.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:21796119

This page was processed by crosslinker on 2026-05-09. - PMID:22343534

This page was processed by crosslinker on 2026-05-09. - PMID:24476821

This page was processed by crosslinker on 2026-05-09. - PMID:25079552

This page was processed by wiki-cli on 2026-05-11. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:27646943

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