MOLECULAR-GENETICS OF APUDOMAS

It is tempting to speculate that genetic studies of the human APUDomas , particularly those of a hereditary nature, may ultimately provide va luable clues to the molecular basis of malignant transformation in cel ls of all types, uncover the mechanisms responsible for tumor progress ion, and perhaps decipher the signals important in the differentiation of normal neural crest-derived tissue. Generally, several strategies have been used in the genetic analysis of these tumors with success. T hese include (1) cytogenetic examination of recurring chromosomal abno rmalities in hopes of pinpointing critical neighboring growth regulato ry sequences important in tumor evolution, (2) identification of domin ant acting oncogenes in tumor cells, (3) search for recessive inactiva ted suppressor genes that may regulate cell growth by analyzing tumors for loss of heterozygosity (LOH), and (4) genetic linkage studies of kindreds affected with familial APUDomas to identify and subsequently characterize the predisposition gene using a positional or functional cloning approach. The results of these strategies as they have been em ployed in the investigation of cutaneous malignant melanoma (CMM), the dysplastic nevus syndrome (DNS), and the multiple endocrine neoplasia (MEN) syndromes are summarized. (C) 1993 Wiley-Liss, Inc.