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NOTCH1
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Interpretation 2262
Tier 3
NOTCH1
Variants
NOTCH1 L2457V
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

NOTCH1 is a transmembrane receptor that plays a role in various cellular processes including cell fate determination, growth, and survival. NOTCH1 may be somatically mutated in a variety of cancers, and these mutations can be either gain- or loss-of-function mutations depending on the tumor type. Translocations and activating somatic mutations in NOTCH1 have been identified in T-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. On the other hand, NOTCH1 loss-of-function somatic mutations are more common in solid tumors, namely squamous cell carcinomas, and occur as missense, frameshift or nonsense mutations. Somatic NOTCH1 mutations are rare in lung adenocarcinoma and are found in about 4% of cases. The NOTCH1 L2457V variant identified in this case has been reported as a benign germline finding in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/380420/). These results should be interpreted in the clinical context.

Citations
  1. Previs RA, et al. Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin Cancer Res 2015;21(5):955-61
  2. Lobry C, et al. Oncogenic and tumor suppressor functions of Notch in cancer: it's NOTCH what you think. J Exp Med 2011;208(10):1931-5
  3. Weng AP, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004;306(5694):269-71
  4. Arruga F, et al. Functional impact of NOTCH1 mutations in chronic lymphocytic leukemia. Leukemia 2014;28(5):1060-70
  5. Nowell CS, et al. Notch as a tumour suppressor. Nat Rev Cancer 2017;17(3):145-159
  6. Lung Adenocarcinoma (TCGA, Provisional): https://tcga-data.nci.nih.gov/docs/publications/tcga/?
Last updated: 2018-06-13 19:00:04 UTC
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