NOTCH3

Overview

NOTCH3 encodes a member of the Notch receptor family involved in cell fate determination and differentiation signaling. In cancer genomics, NOTCH3 alterations have been reported in sarcomas, where missense mutations may contribute to oncogenic signaling.

Alterations observed in the corpus

  • Missense mutations in 14% of RT-UPS vs 4% of sporadic UPS, indicating enrichment in radiation-associated undifferentiated pleomorphic sarcoma PMID:37350195.
  • Identified as a significantly mutated gene in HNSCC whole-exome sequencing of 74 tumor-normal pairs (Broad cohort) PMID:21798893
  • One metatypical sinonasal adenoid cystic carcinoma case harbored a NOTCH3 mutation; referenced alongside NOTCH2 as a Notch-pathway co-actor in AdCC pathogenesis PMID:24418857
  • In PAAD, NOTCH3 alterations occurred at low frequency as part of the 31% NOTCH-pathway alteration in the 109-case exome cohort. PMID:25855536
  • Inactivating mutations (often in the extracellular domain) observed as part of pan-NOTCH inactivation in 25% of human SCLC; mouse models confirm Notch activation suppresses SCLC initiation and prolongs survival. PMID:26168399
  • NOTCH3 was mutated in ATC as part of a finding that all four NOTCH family members (NOTCH1–NOTCH4) were mutated; part of low-frequency hits in a 341-gene panel sequencing study of thyroid cancers PMID:26878173
  • More frequently mutated in HR+ metastatic breast cancer (mBC) than early-stage breast cancer at FDR<0.1; mutations spread across protein domains without obvious hotspots, leaving therapeutic actionability unclear PMID:28027327

Cancer types (linked)

  • MFH (UPS) – NOTCH3 missense mutations enriched in RT-UPS (14%) compared to sporadic UPS (4%) PMID:37350195.

Co-occurrence and mutual exclusivity

  • Not specifically reported in the corpus for NOTCH3 partners PMID:37350195.

Therapeutic relevance

  • No NOTCH3-directed therapy is reported in this corpus PMID:37350195.

Open questions

  • The functional significance of NOTCH3 missense mutations in RT-UPS is not established PMID:37350195.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:21798893

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

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

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