What are other Names for this Test? (Equivalent Terms)
- AUTS9 Mutation Analysis Test
- DFNB97 Mutation Analysis Test
- HGFR Mutation Analysis Test
What is MET Mutation Analysis Test? (Background Information)
- MET mutation refers to an alteration in the MET gene, which is associated with cancers of the liver, kidney, and bone, as well as other disorders
- The MET gene gives instructions for the M10 protein. The M10 protein is a type of receptor tyrosine kinase (RTK). RTKs reside on the surfaces of certain cells, where they act as antennas that receive signals from outside the cell and transmit them inside the cell
- The M10 protein is found on the membranes of liver cells. The signal that the M10 protein recognizes and binds is a chemical hepatocyte growth factor
- Once bound with hepatocyte growth factor, M10 launches a chain of events inside the cell that leads to the growth and division of the cell. M10 is necessary for the survival and movement of cells, and for maintaining the balance of cell populations
- Alterations in the MET gene may result in a defective M10 protein that may activate itself independently of hepatocyte growth factor. The defective M10 is overactive as a result of it no longer needing hepatocyte growth factor to bind, in order to activate
- Alterations in the MET gene that affect M10 protein function may interfere with normal growth and division of cells, causing cancer
- The MET Mutation Analysis Test is a genetic test that helps detect abnormalities in the MET gene. It is used to diagnose cancer. It also aids in the treatment of cancers by guiding selection of therapeutic drugs, including disqualifying certain drugs from use
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 MET Mutation Analysis Test?
Following are the clinical indications for performing the MET Mutation Analysis Test:
- Hearing loss
- Abdominal pain or tenderness, especially in the upper-right part
- Easy bruising or bleeding
- Enlarged abdomen
- Yellow skin or eyes (jaundice)
- Unexplained weight loss
- Blood in the urine, which may appear pink, red, or cola colored
- Back pain just below the ribs that does not go away
- Intermittent fever
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 MET Mutation Analysis Test?
Following is the specimen collection process for MET 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 MET 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 MET Mutation Analysis Test Result?
A positive value for the MET Mutation Analysis Test may disqualify certain therapeutic drugs namely, EGFR-specific TKIs, from being used to treat lung, colorectal, and other cancers. It may also point to a diagnosis of any of the following:
- Nonsyndromic hearing loss and “autosomal recessive 97 hearing loss”
- Hepatocellular carcinoma
- Papillary renal cell carcinoma
- Osteofibrous dysplasia
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:
- MET mutation most notably occurs in a location of the chromosome called 7q31.2 i.e., the long arm (q) of chromosome 7 in position 31.2
- 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)
Chen, Y. B. (2015, August 1). Liver cancer - hepatocellular carcinoma: MedlinePlus Medical Encyclopedia. Retrieved from https://medlineplus.gov/ency/article/000280.htm
Mayo Clinic. (2015, February 13). Kidney cancer Symptoms. Retrieved from http://www.mayoclinic.org/diseases-conditions/kidney-cancer/basics/symptoms/con-20024753
MET gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/MET#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
Keedy, V. L., Temin, S., Somerfield, M. R., Beasley, M. B., Johnson, D. H., McShane, L. M., ... & Giaccone, G. (2011). American Society of Clinical Oncology provisional clinical opinion: Epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non–small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. Journal of clinical oncology, 29(15), 2121-2127.
Arcila, M. E., Oxnard, G. R., Nafa, K., Riely, G. J., Solomon, S. B., Zakowski, M. F., ... & Ladanyi, M. (2011). Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clinical Cancer Research, 17(5), 1169-1180.
Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., ... & Porta, R. (2012). Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. The lancet oncology, 13(3), 239-246.
Koeppen, H., Yu, W., Zha, J., Pandita, A., Penuel, E., Rangell, L., ... & Fu, L. (2014). Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non–small cell lung cancer: MET expression levels are predictive of patient benefit. Clinical Cancer Research, 20(17), 4488-4498.
Singh, R. R., Patel, K. P., Routbort, M. J., Reddy, N. G., Barkoh, B. A., Handal, B., ... & Luthra, R. (2013). Clinical validation of a next-generation sequencing screen for mutational hotspots in 46 cancer-related genes. The Journal of Molecular Diagnostics, 15(5), 607-622.
Tsuta, K., Kozu, Y., Mimae, T., Yoshida, A., Kohno, T., Sekine, I., ... & Tsuda, H. (2012). c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. Journal of Thoracic Oncology, 7(2), 331-339.