Associated Genetic Biomarkers
Notch 3 (NOTCH3) is a gene that encodes a protein that, in Droshophila, functions in the intracellular signaling pathways that are important for neural development. However, the protein's function is not clear in humans. Missense mutations, nonsense mutations, silent mutations, and frameshift deletions and insertions are observed in cancers such as intestinal cancer, skin cancer, and stomach cancer.
NOTCH3 is altered in 3.80% of all cancers with colon adenocarcinoma, lung adenocarcinoma, cutaneous melanoma, breast invasive ductal carcinoma, and endometrial endometrioid adenocarcinoma having the greatest prevalence of alterations .
The most common alterations in NOTCH3 are NOTCH3 Mutation (3.59%), NOTCH3 Amplification (0.34%), NOTCH3 Fusion (0.09%), NOTCH3 Loss (0.04%), and NOTCH3 Deletion (0.04%) .
NOTCH3 status serves as an inclusion eligibility criteria in 4 clinical trials, of which 2 are open and 2 are closed. Of the trials that contain NOTCH3 status as an inclusion criterion, 2 are phase 1 (0 open) and 2 are phase 2 (2 open).
Trials with NOTCH3 status in the inclusion eligibility criteria most commonly target breast carcinoma, adenoid cystic carcinoma, cholangiocarcinoma, and colon carcinoma .
The most frequent alterations to serve as inclusion eligibility criteria are NOTCH3 Amplification, NOTCH3 Fusion, NOTCH3 Mutation, NOTCH3 A1802fs, and NOTCH3 L1515P .
Al101, abemaciclib, carboplatin, cisplatin, and crenigacestat are the most frequent therapies in trials with NOTCH3 as an inclusion criteria .
Significance of NOTCH3 in Diseases
Malignant Solid Tumor +
NOTCH3 is altered in 4.13% of malignant solid tumor patients .
NOTCH3 is an inclusion criterion in 2 clinical trials for malignant solid tumor, of which 0 are open and 2 are closed. Of the trials that contain NOTCH3 status and malignant solid tumor as inclusion criteria, 2 are phase 1 (0 open) .
Breast Carcinoma +
NOTCH3 is altered in 2.67% of breast carcinoma patients .
NOTCH3 is an inclusion criterion in 2 clinical trials for breast carcinoma, of which 1 is open and 1 is closed. Of the trials that contain NOTCH3 status and breast carcinoma as inclusion criteria, 1 is phase 1 (0 open) and 1 is phase 2 (1 open) .
Colon Carcinoma +
Soft Tissue Sarcoma +
Adenoid Cystic Carcinoma +
NOTCH3 is altered in 0.78% of adenoid cystic carcinoma patients .
NOTCH3 is an inclusion criterion in 1 clinical trial for adenoid cystic carcinoma, of which 1 is open and 0 are closed. Of the trial that contains NOTCH3 status and adenoid cystic carcinoma as inclusion criteria, 1 is phase 2 (1 open) .
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.