MEN2A/2B Sequencing for Multiple Endocrine Neoplasia

Background

Thyroid C-cell carcinoma is encountered in three different hereditary diseases: MEN 2A, familial medullary thyroid carcinoma (FMTC), and MEN2B. MEN 2A is a syndrome characterized by medullary thyroid carcinoma (MTC) in almost all gene carriers, pheochromocytoma in ~50% of gene carriers, and hyperparathyroidism in ~20% of gene carriers. Only tumors derived from thyroid C-cells develop in FMTC families. MEN 2B is characterized by MTC and pheochromocytoma.

The RET proto-oncogene was identified as the gene associated with MEN 2A, FMTC and MEN 2B. MEN 2A and FMTC are associated with mutations found primarily in exons 10 or 11 of the RET gene, which encodes a transmembrane-receptor tyrosine kinase. Patients with MEN 2B generally demonstrate mutation in exon 16 within the catalytic core of the tyrosine kinase domain. Less frequent mutations may be found in exons 13, 14 or 15.

OMIM: 171400 / 162300

Clinical Utility

Detection of major mutations in the MEN2A/2B gene that affect Multiple Endocrine Neoplasia. The test is done on peripheral blood specimens for confirmation of clinical diagnosis, carrier status or presymptomatic testing.

Methodology

PCR amplification and Sanger sequencing of exons and flanking intron sequence

Loci Tested

MEN2A/2B exons 10, 11, 13, 14, 15, 16

Specimen Required

Peripheral blood collected in EDTA (purple top) is preferred, 3-10mL.

Turnaround Time

Within 3-5 weeks of receipt

CPT

81405

Shipment Must Include

Specimen
Requisition form
Patient pathology report

References

  1. Lips, C. et al. "Clinical Screening As Compared With DNA Analysis In Families With Multiple Endocrine Neoplasia Type 2A." N Engl. J Med., 331:828-35, 1994.
  2. Landsvater, R. et al. "Mutation Analysis Of The RET Proto-Oncogene In Dutch Families With MEN 2A, MEN 2B and FMTC." Hum Genet., 97: 11-14, 1996.