NRAS

The Pathology Dictionary Team
June 5, 2023

What is NRAS?

NRAS is a gene that provides instructions for making the NRAS protein, which acts as a molecular switch in cell signaling pathways. When activated by external signals, such as growth factors, the NRAS protein sends signals from the cell surface to the nucleus, influencing various cellular processes like cell growth, proliferation, and differentiation.

What is a gene?

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes. Each gene tells the cell how to produce a piece of the machine called a protein.

All genes are made of molecules called bases. There are four bases (A, T, G, and C) that make up the genetic code. The order of the four bases determines which proteins are made.

How does NRAS cause cancer?

In normal, healthy cells, NRAS works with other proteins to regulate cell growth, proliferation, and differentiation. However, a change in the NRAS gene called a mutation can cause the NRAS protein to behave abnormally. Most NRAS mutations result in the production of an NRAS protein which is always active. This uncontrolled activation of the NRAS signaling pathway contributes to the development and progression of cancer.

What types of cancers have NRAS mutations?

NRAS mutations can be found in various types of cancer. Some of the most common cancers associated with NRAS mutations include:

• Melanoma: NRAS mutations are frequently observed in melanoma, a type of skin cancer. It is estimated that around 15-20% of melanomas harbor NRAS mutations.
• Colorectal cancer: NRAS mutations can occur in a subset of colorectal cancers, although they are less common compared to KRAS mutations. NRAS mutations are found in approximately 2-5% of colorectal cancer cases the most common being adenocarcinoma.
• Acute myeloid leukemia (AML): NRAS mutations are relatively common in AML, a type of blood cancer affecting the myeloid cells. It is estimated that around 10-15% of AML cases have NRAS mutations.
• Thyroid cancer: NRAS mutations can be found in a small percentage of thyroid cancers, particularly in follicular thyroid carcinoma and poorly differentiated thyroid carcinoma.
• Lung cancer: Although NRAS mutations are less common than other mutations in lung cancer, they have been reported in a small subset of non-small cell lung cancer (NSCLC) cases including adenocarcinoma.
• Ovarian cancer: NRAS mutations have been detected in a small proportion of ovarian cancers, although they are relatively rare in this cancer type.

How do doctors test for NRAS mutations?

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) is a special type of test that allows pathologists to see the kinds of proteins being made by a cell. Cells with a mutation in the NRAS gene make an NRAS protein that is different from normal cells. Immunohistochemistry can be used to see cells making this abnormal NRAS protein. Positive or reactive means that the tumour cells in your tissue sample are making an abnormal NRAS protein. Negative or non-reactive means that no abnormal NRAS protein was found.

Polymerase chain reaction (PCR)

Polymerase chain reaction (PCR) is a special test that allows pathologists to analyze the bases in one or more genes. By reading the bases in a gene, your pathologist can find cancer-causing mutations.

If a mutation is found in the NRAS gene it will be described in your report as detected or positive. Your report may also say where in the gene the mutation was found. If no mutation is found it will be described in your report as not detected or negative.

Next-generation sequencing (NGS)

Next-generation sequencing (NGS) is a special test used to analyze a large number of genes at the same time. NGS is commonly used to look for mutations in the NRAS gene and other genes that are known to cause cancer.

If a mutation is found it will be described as positive. The location and type of mutation may also be described in your report. A mutation known to cause cancer may be described as pathogenic or likely pathogenic. If no mutation is found, the results will be described as negative.