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Tissue Selectivity in Multiple Endocrine Neoplasia Type 1-Associated Tumorigenesis

¹ Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University; Departments of ² Physiological Chemistry, ³ Internal Medicine and Endocrinology, ⁴ Medical Genetics, and ⁵ Metabolic and Endocrine Diseases, University Medical Center Utrecht; and ⁶ Netherlands Metabolomics Center, Utrecht, The Netherlands

Requests for reprints: Jo W. M. Höppener, Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. Phone: 31-88-75-549-87; Fax: 31-88-75-54295; E-mail: J.W.M.Hoeppener{at}umcutrecht.nl.

The phenotype of the multiple endocrine neoplasia type 1 (MEN1) syndrome cannot be explained solely by the expression pattern of the predisposing gene MEN1 and its encoded protein, menin. This review addresses putative factors determining MEN1-associated tissue-selective tumorigenesis. Menin's interaction with mixed-lineage leukemia protein-containing histone methyl transferase (MLL-HMT) complex mediates tissue-selective tumor-suppressing and tumor-promoting effects of menin, and as such could be decisive for the predisposition of individual tissues to MEN1-associated tumorigenesis. In tissues in which menin acts as a tumor suppressor, tumorigenesis could depend on the inability of such tissues to adequately compensate for MEN1 gene loss, whereas the variable clinical presentation of MEN1 in individual patients could be a reflection of additional epigenetic factors and/or modifier genes. Further research on this topic may facilitate development of novel therapeutic strategies that could prevent or delay the onset of MEN1-associated tumorigenesis. [Cancer Res 2009;69(16):6371–4]