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HelpTest ID RETZ RET Proto-Oncogene, Full Gene Analysis
Useful For
Confirmation of suspected clinical diagnosis of multiple endocrine neoplasia type A or B, Hirschsprung disease, or congenital central hypoventilation syndrome in patients with a suspected diagnosis of any of these conditions
Identification of familial RET mutation to allow for predictive or diagnostic testing in family members
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Amplification Followed by DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name
RET Gene, Full Gene AnalysisSpecimen Type
VariesSpecimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: Specimen preferred to arrive within 96 hours of collection.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Forms:
1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.
2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions
3. If not ordering electronically, complete, print, and send an Oncology Test Request Form (T729) with the specimen
(http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
Clinical Information
Mutations in the RET proto-oncogene are associated with 3 distinct, and in rare cases, overlapping clinical syndromes.
Multiple endocrine neoplasia type 2 (MEN2):
MEN2 is an autosomal dominant cancer syndrome that has classically been divided into 3 subtypes: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The characteristic features of MEN 2A include multifocal medullary thyroid carcinoma (MTC), bilateral pheochromocytoma, and primary hyperparathyroidism. MEN 2B is characterized by MTC, pheochromocytoma, and multiple mucosal neuromas. Other features of MEN 2B include enlarged nerves of the gastrointestinal tract (ganglioneuromatosis), marfanoid habitus, hypotonia, and corneal nerve thickening. FMTC has traditionally been diagnosed in families with 4 or more cases of MTC in the absence of pheochromocytoma or parathyroid involvement. Early diagnosis of thyroid cancer and appropriate surgical intervention can prevent metastatic MTC and can reduce the morbidity and mortality associated with MTC. The majority of MEN2-related mutations occur at conserved cysteine residues within exons 10 and 11. Additional mutations in exons 13, 14, 15, and 16 account for the majority of other MEN2-related RET mutations. Taken together, mutations in these codons account for approximately 98% of MEN 2A, >99% of MEN2B, and 96% of FMTC.
Hirschsprung disease (HSCR):
HSCR is a congenital disorder of impaired intestinal motility, also known as aganglionic megacolon. Variable lengths of the colon may be affected, resulting in either total aganglionosis, long-segment HSCR, or short-segment HSCR. HSCR affects approximately 1 in 5,000 live births and is resolved via surgical intervention.
Although gain of function mutations in RET may result in MEN2, loss of function mutations have been reported in patients with Hirschsprung disease (HSCR). It has been reported that up to 50% of familial cases of HSCR and 3% to 35% of sporadic HSCR are due to RET germline mutations. However, most of the mutations that cause HSCR occur outside of the codons that are typically mutated in MEN2.
Congenital central hypoventilation syndrome (CCHS):
CCHS is a congenital disorder of autonomic nervous system dysfunction in which individuals hypoventilate during sleep, and less commonly while awake. While not the primary etiology of disease, RET mutations have been associated with CCHS; in addition, RET mutations may be modifiers of CCHS development in individuals with HSCR.
Co-occurrence of HSCR and CCHS is more commonly observed than the co-occurrence of MEN2 with either HSCR or CCHS.
Reference Values
An interpretive report will be provided.
Cautions
Some individuals who have a diagnosis of multiple endocrine neoplasia type A or B, Hirschsprung disease, or congenital central hypoventilation syndrome and/or involvement of RET may have a mutation that is not identified by this method (eg, large genomic deletions or duplications, promoter mutations, deep intronic mutations). The absence of a mutation, therefore, does not eliminate the possibility of a diagnosis of multiple endocrine neoplasia type A or B, Hirschsprung disease, or congenital central hypoventilation syndrome. For predictive testing of asymptomatic individuals, it is important to first document the presence of an RET gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Day(s) Performed
Performed weekly, varies
Report Available
14 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
81406- RET (ret proto-oncogene) (eg, Hirschsprung disease), full gene sequence