Molecular Diagnostic Laboratory
Phone: (314) 454-8685; 454-7601
FAX: (314) 454-7616
Barbara Zehnbauer, PhD FACMG
Multiple Endocrine Neoplasia (MEN2), Familial Medullary Thyroid Carcinoma (FMTC)
Screen for multiple RET Mutations on exons 10, 11, 13, 14, and 16
Indications for Molecular Testing
• Confirmation of diagnosis of MEN 2A, FMTC, and MEN 2B.
• Presymptomatic screening of family members at risk.
• Identification of germline mutations to distinguish sporadic from familial medullary thyroid carcinoma.
The molecular diagnostic assay for detection of RET MEN2A or MTC mutations involves PCR amplification of the
exons 10,11, 13, and 14 followed by direct DNA sequencing of the PCR product. If the patient is suspected of
having MEN2B then polymerase chain reaction (PCR) amplification followed by restriction fragment length
polymorphism (RFLP) analysis of exon 16 is performed.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Interpretation of DNA Analysis
Mutations in the RET proto-oncogene are associated with predisposition for development of medullary thyroid
carcinoma (MTC), pheochromocytoma (adrenal cancer), and/or parathyroid tumors. These cancers can be
inherited in families with a history of multiple endocrine neoplasia (MEN2) or familial MTC (FMTC). Mutations are
localized to a few recurrent sites within the RET gene. In exons 10 and 11, mutations in five conserved cysteine
codons (609, 611, 618, 620, and 634) can cause MEN2A, FMTC, or sporadic MTC. Rare mutations in exons 13
(codons 768, 790, and 791, glutamine) and 14 (codon 804, valine) may be found in some FMTCs and sporadic
MTCs. Finally, a mutation in exon 16 (codon 918, methionine) can cause MEN2B. Identification of one specific
point mutation in an affected family member of a MEN2 or FMTC kindred allows screening of other at-risk
relatives for the same disease-associated genetic alteration. Greater than 95% of individuals with RET mutations
in these regions will develop one or more of these tumor types. Relatives who are negative for the presence of
these germline RET mutations will have a greatly reduced risk of MTC thus avoiding the discomfort and potential
side-affects of physiological monitoring and/or unnecessary endocrine surgery. .
Peripheral Blood--1 lavender-top (EDTA) tube. Invert several times to mix blood. Do not freeze, forward
promptly at ambient temperature to the following address:
Molecular Diagnostic Laboratory
Clinical information must be
Barnes-Jewish Hospital North, Room 2320
provided with specimen referral
Mail Stop 90-35-709 to correctly interpret test results.
216 South Kingshighway
St. Louis, MO 63110
Available from BJH Laboratory Customer Service at 314-362-1470;
Comprehensive test of affected individual (exons 10, 11, 13, and 14)
Follow-up test for a known mutation (at-risk for known, kindred mutation or MEN 2B single mutation)
CPT codes for MEN 2A comp: 83907, 83890, 83898 x4, 83894, 83891 x4, 83904 x4, 83912. MEN 2A follow-up: 83907,
83890, 83898, 83894, 83891, 83904, 83912. MEN 2B: 83907, 83890, 83898 x2, 83892 x2, 83894 x2, 83912.
Donis-Keller, H., et al.; Mutations in the RET proto-oncogene are Associated with MEN2A and FMTC. Hum. Mol. Genet.
Jimenez, C and RF Gagel . Genetic testing in endocrinology: lessons learned from experience with MEN2. Growth Hormone
and IGF Research 14: 5150-5157, 2004.