At a glance

Also known as

MEN2A, MEN2B, MTC1, PTC, Ret proto-oncogene, Hirschsprung disease

Why get tested?
A doctor may request testing of the RET gene in patients with various types of caner, including familial medullary thyroid carcinoma, multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B), pheochromocytoma and parathyroid hyperplasia. The RET gene mutations can also cause a non-cancerous condition called Hirschsprung disease which results in severe constipation or blockage of the intestine.
When to get tested?
Testing is often requested by a specialist doctor, usually a Clinical Geneticist after referral from an oncologist.
Sample required?
3 millilitres of blood collected into a tube containing an EDTA anticoagulant.

What is being tested?

How is the sample collected for testing?
Blood is collected from a vein on the inside of the elbow using a needle and syringe.
Is any test preparation needed to ensure the quality of the sample?

The Test

How is it used?

Different mutations in the DNA sequence of the RET gene are associated with different clinical conditions. See below for more information.

When is it requested?

Testing is requested by the specialist doctor when the RET gene is suspect to be the cause of the clinical symptoms.

What does the test result mean?

If a RET gene mutation is found in a patient with familial medullary thryoid carcinoma, multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B), pheochromocytoma and parathyroid hyperplasia it is most likely the cause of the disease.

Mutations responsible for these conditions result in an overactive RET protein that triggers cells to grow and divide abnormally, and lead to the formation of tumours.

Everyone has two copies of the RET gene. Each of these are randomly inherited from our parents. DNA mutations in one copy of the RET gene can increase the risk of developing tumours that may be cancerous or non-cancerous depending on the specific RET gene mutation that has been inherited.

The risk of developing MEN2A if you have inherited the familial mutation is 95-100%, up to 50% for pheochromocytoma, and up to 30% for hyperparathyroidism. For MEN2B, the risk is 95-100% and up to 50% for pheochromocytoma. For FMTC the risk is 95-100%. The specific RET gene mutation will determine which subtype of tumour the patient will have and may provide more information on the cancer risks.

Hirschsprung disease:
Depending on the type of RET gene mutation there could be an increased risk for Hirschsprung disease (a non-cancerous condition) in addition to, or instead of the cancer risks mentioned above. In this condition, the genetic changes result in a non-functioning version of the RET protein that cannot communicate with other cells. and causes certain nerves within the intestine to not develop properly.

Is there anything else I should know?

Treatment of people with RET mutations:
Prophylactic thryoidectomy, where the thyroid gland is removed prior to the development of cancer, is a common form of treatment to avoid cancer. Once a tumour has been detected the thyroid gland is removed to prevent the spread of the cancer. Screening people at risk of developing these cancers can begin in early childhood with an annual physical examination, imaging and blood tests. There are drug trials underway that inhibit the RET protein function but non have yet been approved for clinical use.

Family Members: Relatives (such as parents, brothers, sisters, children) have a 50% chance of inheriting the same RET mutation as do other family members (aunts, uncles, cousins). Once a mutation has been detected in a family member, all relatives can easily be tested for this same mutation. If a person in the family does not have the familial mutation then they do not have an increased risk of developing cancer that is greater than te general population.

Prenatal Testing:
As children of affected individuals have a 50% chance of inheriiting a pathogenic RET gene mutation, prenatal testing of pregnancies is possible if the RET pathogenic variant has been identified in an affected family member. This testing is done on DNA extracted from amniotic fluid or a biopsy sampe from the placenta called a Chorionic Villus sample (CVS).
An alternative method of testing is to use Preimplantation Genetic Diagnosis (PGD). Testing of the RET gene is performed on day 5 embryos that has been generated by IVF, and those not carrying the familial mutation are implanted.

It is recommended that this information is shared with family members so they can discuss the implications with their doctors.

Common Questions

Is there a Medicare rebate for RET gene testing?

Yes, there is a rebate for the detection of mutations in the RET gene in patients with suspected clinical diagnosis of multiple endocrine neoplasia type 2 (MEN2).

Last Review Date: January 10, 2023

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