Molecular genetics of neuroendocrine tumors

Neuroendocrine tumors can develop either sporadically or in association with familial syndromes such as multiple endocrine neoplasia type I (MEN I), multiple endocrine neoplasia type 2 (MEN2) or von Hippel-Lindau (VHL). A variety of genetic approaches has been utilized to dissect the underlying molecular pathogenesis of these distinctive tumors, including genome-wide screens such as comparative genomic hybridization, loss of heterozygosity and DNA microarray analysis as well as targeted investigations into specific tumor suppressor gene and oncogene candidates. The identification of the MEN I tumor suppressor gene that underlies the MEN I syndrome has provided important new insights into tumor pathogenesis. In addition, a number of independent approaches has converged on a pivotal role for regulators of the cell cycle. However, our understanding of the molecular biology of these tumors remains far from complete. In this review we highlight some of the key approaches, findings and implications of these genetic studies.