Multiple endocrine neoplasia type 2

Abstract

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominantly inherited tumor syndrome subclassified into three distinct syndromes: MEN 2A, MEN 2B and familial medullary thyroid carcinoma. In MEN 2 families, medullary thyroid carcinoma, pheochromocytomas and parathyroid adenomas occur with a variable frequency, also depending on the specific genetic defect involved. In 1993, the responsible MEN2 gene was identified. The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. The germline RET mutations result in a gain-of-function of the RET protein. Extensive studies on large families revealed that there is a strong genotype–phenotype correlation. In this review, guidelines for early diagnosis, including MEN2 gene mutation analysis, and treatment, including preventive surgery, periodic and clinical monitoring, have been formulated, enabling improvement of life expectancy and quality of life. Identification of the RET protein has also provided new insights into its function, and the specific pathways it effects involved in cell proliferation, migration, differentiation and survival. In the near future, identification of biological tumor markers will enable target-directed intervention and may prevent and/or delay progression of both primary and residual tumor growth.

Keywords::

• DNA diagnosis
• genetic testing
• MEN 2
• multiple endocrine neoplasia type 2
• mutation analysis
• periodic clinical monitoring
• presymptomatic treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

FMTC: Familial medullary thyroid carcinoma; MEN 2: Multiple endocrine neoplasia type 2; MTC: Medullary thyroid carcinoma; PC: Pheochromocytoma.