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NOTCH1 Mutation Analysis Test

Last updated May 31, 2017

Approved by: Maulik P. Purohit MD MPH

The NOTCH1 Mutation Analysis Test is a genetic test that detects abnormalities in the NOTCH1 gene. It is used to diagnose skin disorders, heart disease, and various other disorders and cancers.

What are other Names for this Test? (Equivalent Terms)

  • AOVD1 Mutation Analysis Test
  • Neurogenic Locus Notch Homolog Protein 1 Mutation Analysis Test
  • Translocation-Associated Notch Protein TAN-1 Mutation Analysis Test

What is NOTCH1 Mutation Analysis Test? (Background Information)

  • NOTCH1 mutation refers to an alteration in the NOTCH1 gene, which is associated with skin, heart, immune system, and other cancers and disorders
  • The NOTCH1 gene gives instructions for the Notch1 protein. Notch1 helps cells communicate with each other. It is a receptor protein found on the surfaces of cells
  • As a receptor, Notch1 acts like an antenna. It recognizes signals from outside the cell and transmits them inside the cell, where they may cause changes in growth, division, metabolism, and even cause self-destruction
  • Notch1 is an important receptor. It is capable of both causing and preventing cancer. It is also important for the growth and maintenance of various organs, such as the heart and skin, before and after birth
  • An alteration in the NOTCH1 gene may result in a Notch1 protein that is defective. This may have widespread effects, including resulting in cancer and abnormal tissue development
  • The NOTCH1 Mutation Analysis Test is a genetic test that detects abnormalities in the NOTCH1 gene. It is used to diagnose skin disorders, heart disease, and various other disorders and cancers

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization techniques, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another.

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the NOTCH1 Mutation Analysis Test?

Following are the clinical indications for performing the NOTCH1 Mutation Analysis Test: 

  • Abnormal development
  • Skin problems, including missing patches of skin
  • In newborns:
    • Loss of healthy skin color.
    • Cyanosis (a bluish tint to the skin, lips, and fingernails)
    • Rapid or troubled breathing.
    • Swelling or puffiness in the face, hands, feet, legs, or areas around the eyes
    • Shortness of breath
    • Tiring easily during feedings
  • Heart problems during developmental years

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • If there is a family history of the medical disorder/condition
  • To distinguish other conditions that have similar features (signs and symptoms)
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for NOTCH1 Mutation Analysis Test?

Following is the specimen collection process for NOTCH1 Mutation Analysis Test:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Peripheral blood in individuals showing signs and symptoms suspected of TTT
    • In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
    • Fresh tumor tissue during biopsy: In some cases, the testing can be performed on tumor tissue also
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility


  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of NOTCH1 Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the NOTCH1 Mutation Analysis Test Result?

A mutation in the NOTCH1 gene indicates a positive result for the NOTCH1 Mutation Analysis Test. This may point to a diagnosis of any of the following:

  • Adams-Oliver syndrome
  • Critical congenital heart disease
  • Head and neck squamous cell carcinoma (HNSCC)
  • T-cell acute lymphoblastic leukemia
  • Chronic lymphocytic leukemia
  • Thoracic aortic aneurysm

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • MYD88 mutation most notably occurs in a location of the chromosome called 9q34.3 i.e., the long arm (q) of chromosome 9 in position 34.3
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:



Please visit our Laboratory Procedures Center for more physician-approved health information:


References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

Critical congenital heart disease | Baby's First Test | Newborn Screening | Baby Health. (n.d.). Retrieved from http://www.babysfirsttest.org/newborn-screening/conditions/critical-congenital-heart-disease-cchd

NOTCH1 gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/NOTCH1#location

Helpful Peer-Reviewed Medical Articles:

Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)

Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Agrawal, N., Frederick, M. J., Pickering, C. R., Bettegowda, C., Chang, K., Li, R. J., ... & Zhang, N. (2011). Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science, 333(6046), 1154-1157.

Rossi, D., Rasi, S., Fabbri, G., Spina, V., Fangazio, M., Forconi, F., ... & Monti, S. (2011). Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood, blood-2011.

Villamor, N., Conde, L., Martínez-Trillos, A., Cazorla, M., Navarro, A., Bea, S., ... & Rozman, M. (2013). NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia, 27(5), 1100-1106.

Zuurbier, L., Homminga, I., Calvert, V., te Winkel, M. L., Buijs-Gladdines, J. G. C. A. M., Kooi, C., ... & Horstmann, M. (2010). NOTCH1 and/or FBXW7 mutations predict for initial good prednisone response but not for improved outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on DCOG or COALL protocols. Leukemia, 24(12), 2014-2022.

Oscier, D. G., Rose-Zerilli, M. J., Winkelmann, N., de Castro, D. G., Gomez, B., Forster, J., ... & Else, M. (2013). The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood, 121(3), 468-475.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 31, 2017
Last updated: May 31, 2017