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HRAS Mutation Analysis Test

Last updated Feb. 1, 2017

The HRAS Mutation Analysis Test is a genetic test to detect abnormalities in the HRAS gene. It is used to diagnose cancers. It also aids in the treatment of cancer by guiding selection of therapeutic drugs, including disqualifying certain drugs from use.


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

  • Harvey Rat Sarcoma Viral Oncogene Homolog Mutation Analysis Test
  • RASH_HUMAN Mutation Analysis Test
  • Transforming Protein P21/H-RAS-1 (C-H-RAS) Mutation Analysis Test

What is HRAS Mutation Analysis Test? (Background Information)

  • HRAS mutation refers to an alteration in the HRAS gene. It is associated with a wide variety of cancers, including of kidney, skin, thyroid, brain, and bone
  • The HRAS gene gives instructions for the H-Ras protein. H-Ras is involved in cellular communication
  • It receives signals from receptor proteins on the membranes of cells, and relays those signals inside the cell to tell the cell to divide or to self-destruct; a process called apoptosis
  • Abnormalities in the HRAS gene may lead to a defective H-Ras protein that is always on. In this state, H-Ras continuously tells the affected cell to divide. This may make the cell cancerous
  • The HRAS Mutation Analysis Test is a genetic test to detect abnormalities in the HRAS gene. It is used to diagnose cancers. It also aids in the treatment of cancer 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 technique, 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.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 HRAS Mutation Analysis Test?

Following are the clinical indicators for performing the HRAS Mutation Analysis Test: 

  • Fever
  • Fatigue
  • Body pain, pain due to gas
  • Change in appetite
  • Unexplained weight change
  • Nausea, vomiting
  • Skin changes
  • Cramps
  • Bloating
  • Irregular bowel movements; constipation, diarrhea
  • Rectal bleeding, bloody stools
  • Anemia
  • Jaundice
  • Frequent urination, blood in urine

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

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • 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 the HRAS Mutation Analysis Test?

Following is the specimen collection process for HRAS 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:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumorfixed 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

Note:

  • 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 HRAS 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 HRAS Mutation Analysis Test Result?

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

  • Bladder cancer
  • Costello syndrome
  • Epidermal nevus
  • Squamous cell carcinoma
  • Thyroid cancer
  • Kidney cancer

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:

  • HRAS mutation most notably occurs in a location of the chromosome called 11p15.5 - i.e., the short arm (p) of chromosome 11 in position 15.5
  • 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 of 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.misdiagnosis.

What are some Useful Resources for Additional Information?

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

http://www.dovemed.com/diseases-conditions/bladder-cancer/

http://www.dovemed.com/diseases-conditions/epidermal-nevus-en/

http://www.dovemed.com/diseases-conditions/squamous-cell-carcinoma-skin/

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

http://www.dovemed.com/common-procedures/procedures-laboratory/

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)

Cancer Symptoms – Diagnosing Specific Cancer Types | CTCA. (n.d.). Retrieved from http://www.cancercenter.com/terms/cancer-symptoms/?source=GGLPS01&channel=paid+search&invsrc=Non_Branded_Paid_Search_Google_General_Search&utm_device=c&utm_budget=Corporate&utm_site=GOOGLE&utm_campaign=Non+Brand%3ETop+Terms&utm_adgroup=Symptoms%3ECancer+Symptoms%3EExact&utm_term=cancer+symptoms&utm_matchtype=e&k_clickid=98466eec-8a1b-4205-b961-85a94b52d8ca&k_profid=422&k_kwid=325976

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

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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

Deeb, K. K., Hohman, C. M., Risch, N. F., Metzger, D. J., & Starostik, P. (2015). Routine Clinical Mutation Profiling of Non–Small Cell Lung Cancer Using Next-Generation Sequencing. Archives of Pathology and Laboratory Medicine, 139(7), 913-921.

Allory, Y., Beukers, W., Sagrera, A., Flández, M., Marqués, M., Márquez, M., ... & Carrato, A. (2014). Telomerase reverse transcriptase promoter mutations in bladder cancer: high frequency across stages, detection in urine, and lack of association with outcome. European urology, 65(2), 360-366.

Piana, S., Ragazzi, M., Tallini, G., De Biase, D., Ciarrocchi, A., Frasoldati, A., & Rosai, J. (2013). Papillary thyroid microcarcinoma with fatal outcome: evidence of tumor progression in lymph node metastases: report of 3 cases, with morphological and molecular analysis. Human pathology, 44(4), 556-565.

Chiosea, S. I., Miller, M., & Seethala, R. R. (2014). HRAS mutations in epithelial–myoepithelial carcinoma. Head and neck pathology, 8(2), 146-150.

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 1, 2017
Last updated: Feb. 1, 2017