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9q34.3 HGNC:7881 MIM.190198

Wednesday 11 June 2003

Definition: Notch receptors (NOTCHs) are highly conserved single-pass transmembrane proteins that regulate cellular differentiation and tissue homeostasis in a context-dependent manner and are implicated in normal development and in oncogenesis.

Upon interaction with Notch ligands on neighboring cells, signal transduction by Notch receptors occurs through a series of proteolytic cleavages.

The last of these is mediated by a [gamma]-secretase complex, which liberates the intracellular domain (ICD) of Notch to allow it to translocate to the nucleus and influence transcription of target genes. There are 4 Notch receptors (Notch 1 to 4) in mammals.

NOTCH1 is the best-characterized member and was initially discovered from cases of human T-LBL harboring t(7;9)(q34;q34.3), which juxtaposes the NOTCH1 gene on chromosome 9 to T-cell receptor [beta]-enhancer/promoter elements on chromosome 7.

Subsequent studies have shown a critical role for Notch1 in normal T-cell differentiation, being both necessary and sufficient for development from hematopoietic stem cells.


- NOTCH1 germline mutations in bicuspid aortic valve (16729972)

- NOTCH1 is aberrantly activated in more than 50% of patients with acute lymphoblastic T-cell leukaemia (T-ALL).

- A subset of T-cell acute lymphoblastic leukemias is associated with a recurrent t(7;9)(q34;q34) translocation involving human NOTCH1.

- MIR143-NOTCH1 gene fusions in benign and malignant glomus tumors (23999936) See MIR143

Diagnostic use

- NOTCH1 Intracellular Domain Immunohistochemistry as a Diagnostic Tool to Distinguish T-Lymphoblastic Lymphoma From Thymoma. ( 25517959)

  • The NOTCH1 signaling pathway is frequently activated in T-LBL and plays a central role in the pathogenesis of this disease.
  • Antibodies to NOTCH1 intracellular domain (N1ICD), recognizing the active form of NOTCH1, have been developed.
  • Normal thymocytes do not express significant levels of N1ICD.
  • Thymomas are negative for N1ICD, whereas a high percentage of T-LBL expresses N1ICD.
  • N1ICD immunohistochemistry appears to be a useful method in distinguishing T-LBL from thymoma.

See also



- NOTCH1 Intracellular Domain Immunohistochemistry as a Diagnostic Tool to Distinguish T-Lymphoblastic Lymphoma From Thymoma. Jegalian AG, Bodo J, Hsi ED. Am J Surg Pathol. 2015 Apr;39(4):565-72. doi : 10.1097/PAS.0000000000000358 PMID: 25517959

- Clinical and biologic characterization of T-cell Neoplasias with rearrangements of chromosome 7 band q34. Smith S, Morgan R, Gemmell R , Amylon M, Link M, Linker C, Hecht B Warnke R, Hecht F. Blood 1988 ; 71(2): 395-402. PMID 2962650

- TAN-1 the human homolog of the Drosophilia notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, SKLAR J. Cell 1991; 66(4) : 649-661. PMID 1831692

- T cell leukemia-associated human Notch homologue has I Kappa B-like activity and physically interacts with nuclear-factor-kappa B proteins in T cells.Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T.
J Exp Med 1996 ; 183(5) : 2025-2032. PMID 8642313

- Essential roles for ankyrin repeats as transactivation domains in induction of T cell leukemia by Notch1. Aster JC, Xu l, Karnell FG, Patriub V, Pui JC, Pear WS. Molecular and Cellular Biology 2000; 20(20) : 7505-7515. PMID 11003647

- Neoplastic transformation by Notch requires nuclear localization. Jeffries S, Capabianco AJ. Mol Cell Biol 2000; 20(11) : 3928-3941. PMID 10805736