RAS (KRAS and NRAS, all RAS) testing
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
RAS (KRAS and NRAS, all RAS) testing detects mutations in the KRAS and NRAS genes using a sample of tumour tissue obtained during a biopsy or surgery, and sometimes a blood sample. It is used to help guide cancer treatment—most commonly in colorectal cancer—by determining whether targeted therapies are likely to be effective.
Why get tested?
To determine whether a cancer, usually a large bowel (colorectal) cancer is positive for KRAS or NRAS gene mutation, which helps to guide treatment and determine outcome. Cancer cells can grow and spread due to the changes (mutation) in the RAS gene. The RAS gene is like a hidden message that tell cells what to do. RAS gene mutation analysis is also used in the assessment of some other cancer types including non-small cell lung cancer (NSCLC), head and neck cancer.
When to get tested?
If you have been diagnosed with a cancer and your doctor wants to determine whether the KRAS and NRAS genes are mutated in the tumour. If the KRAS or NRAS genes are mutated, the cancer will not be responsive to treatment with RAS targeted therapy.
Sample required?
A sample of cancer tissue obtained during a biopsy or surgical excision. Generally this test is done on the biopsy taken for initial diagnosis and a second biopsy is not necessary.
Test preparation needed?
None
What is being tested?
The biopsy or resection specimen tissue are stored by the pathology laboratory for at least ten years. The tissues/cells are embedded (moulded) in paraffin wax block. This means that the test can be undertaken on this “archive” material at any stage in the future if disease becomes evident at a different place in the body (metastatic disease).
Testing for RAS gene mutations is very important in determining the best form of treatment for metastatic colon and rectum (colorectal) cancer, also called stage four colorectal cancer. RAS is involved in passing signals within tumour cells which result in growth of the tumour. The gene which is responsible for RAS signalling occurs in two different forms; mutated (abnormal) and wild-type (normal).
Approximately 40% of patients with metastatic colon cancer have a tumour with a mutated RAS gene. These patients are unlikely to respond to treatment with anti-epidermal growth factor receptor therapies such as cetuximab and panitumumab. Treatment using these drugs is not recommended for patients with mutated RAS gene as they would suffer from unwanted side effects of the drug without getting any benefit.
Patients with metastatic disease who have normal (wild-type) RAS genes are likely to respond to either cetuximab or panitumumab.
In the UK, RAS gene testing is recommended in all patients with metastatic colorectal cancer. There is a good correlation between RAS gene mutation status in the primary tumour and metastases. Stored biopsies or resection specimens of the primary tumour taken months or years before the onset of metastatic disease can be tested for RAS gene mutation at a later date.
Recently, mutated KRAS genes in advanced non-small cell lung cancer, has been shown to respond to sotorasib (Lumykras) targeted treatment. Sotorasib works by binding to the abnormal KRAS G12C to stop the cancer cell from dividing and growing. About 13% of non-small cell lung cancers have the KRAS G12C mutation.
How is the sample collected for testing?
A sample of cancer tissue is obtained by doing a fine needle aspiration, needle biopsy, or surgical biopsy/excision
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
Common questions
Patients with metastatic colon cancer and wild-type (normal) RAS gene status may be offered treatment with drugs such as cetuximab (Erbitux) and panitumumab (Vectibix). These drugs are known as epidermal growth factor receptor (EGFR) inhibitors. Those patients who have the abnormal (mutated) RAS gene will not derive benefit from treatment with these agents.
RAS mutation testing is recommended as part of the workup of patients with metastatic colorectal cancer. It helps the doctor determine treatment options and understand more about the cancer’s characteristics.
Patients whose tumours have a mutated RAS gene are unlikely to respond to treatment with anti-epidermal growth factor receptor therapy such as cetuximab and panitumumab. Patients with metastatic disease with wild-type (normal) RAS genes are likely to respond to these treatments, which improve the overall response to chemotherapy.
“All-RAS” testing (testing for both KRAS and NRAS) is currently the only additional test that oncologists will routinely request if metastatic disease is found.
No, tumours often respond to conventional chemotherapy. However, the improved response which is seen in some patients with the addition of epidermal growth factor receptor inhibitors will not be seen in patients with mutated RAS genes. This additional treatment is not indicated in patients with mutated RAS genes.