The MEN1 gene is a likely tumor suppressor gene because tumors in multiple endocrine neoplasia type 1 (MEN1) show loss of heterozygosity (LOH) about the MEN1 locus and because sporadic tumors of the same tissues also show 11q13 LOH implicating loss of this gene through a similar mechanism. We have helped to lead an intramural NIH collaboration that has cloned the MEN1 gene. We are continuing to explore its clinical and its basic implications. We have proven that MEN1 inactivation causes nonendocrine tumors (angiofibroma, collagenoma, and leiomyoma) in MEN1. We find germline mutations in 70-80% of probands with the rare syndromes of familial MEN1 or with sporadic MEN1. Pobands with familial isolated hyperparathyroidism have rarely shown MEN1 mutations. We will continue to explore these and other MEN1-like states with rare germline MEN1 mutations. The definition of subgroups that are deficient of MEN1 mutation has promoted the identification of known genes (CASR, p27) and newly identified genes (HRPT2, AIP, p15, p18, p27) in MEN1-like states. We have also found somatic MEN1 mutation in 15 to 35% of sporadic tumors of many endocrine organs. Its role in common tumors predicts that clarification of its molecular pathway will offer new chances for interventions in many common variety tumors. A mouse strain was engineered with MEN1 heterozygous inactivation. Loss of the normal allele of MEN1 caused giant hyperplasia of pancreatic islets. This is a polyclonal process without loss of menin. This is a phenotype that arises probably from loss of one allele of MEN1 or haploinsufficiency. It is likely a tumor precursor stage and it has implications about islet development.
| Marx, Stephen J (2014) Uncoupling of secretion from growth in some hormone secretory tissues. J Clin Endocrinol Metab 99:4051-9 |
| Gluick, Thomas; Yuan, Ziqiang; Libutti, Steven K et al. (2013) Mutations in CDKN2C (p18) and CDKN2D (p19) may cause sporadic parathyroid adenoma. Endocr Relat Cancer 20:L27-9 |
| Marx, Stephen J (2013) Multiplicity of hormone-secreting tumors: common themes about cause, expression, and management. J Clin Endocrinol Metab 98:3139-48 |
| Simonds, William F; Varghese, Sarah; Marx, Stephen J et al. (2012) Cushing's syndrome in multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf) 76:379-86 |
