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 3.62% of all cancers with colon adenocarcinoma, lung adenocarcinoma, cutaneous melanoma, breast invasive ductal carcinoma, and melanoma having the greatest prevalence of alterations .
The most common alterations in NOTCH3 are NOTCH3 Mutation (2.97%), NOTCH3 Amplification (0.19%), NOTCH3 A1802Gfs*8 (0.02%), NOTCH3 Loss (0.02%), and NOTCH3 A284T (0.02%) .
NOTCH3 status serves as an inclusion eligibility criteria in 3 clinical trials, of which 1 is open and 2 are closed. Of the trials that contain NOTCH3 status as an inclusion criterion, 2 are phase 1 (0 open) and 1 is phase 2 (1 open).
Trials with NOTCH3 status in the inclusion eligibility criteria most commonly target adenoid cystic carcinoma, breast carcinoma, cholangiocarcinoma, and colon carcinoma .
The most frequent alterations to serve as inclusion eligibility criteria are NOTCH3 A1802fs, NOTCH3 Amplification, NOTCH3 Fusion, NOTCH3 L1515P, and NOTCH3 Mutation .
Al101, ly3039478, abemaciclib, carboplatin, and cisplatin 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 3.64% 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) .
Colon Carcinoma +
Breast Carcinoma +
Soft Tissue Sarcoma +
Adenoid Cystic Carcinoma +
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 6. This dataset does not represent the totality of the genetic landscape; see paper for more information.