Prologue to the volume: Endocrine tumors and their genetics, a perspective.

Abstract

Although endocrine tumors (or their consequences) have been known since the beginning of history (1, 2), familial predisposition to these lesions was described only in the last 70 years (3). The term endocrine (MEN) was introduced only relatively recently, in 1968, although Dr. Wermer had suggested the term multiple endocrine adenoma in 1954 (3). A series of meetings on multiple endocrine neoplasias (MEN) have documented the extraordinary progress of the field in the modern era (4–6). We got a glimpse of what modern genetics is able to do when Neumann et al. described one of the classic RET oncogene mutations in a family afflicted by inherited pheochromocytoma since the 1890’s (7). Certainly, multiple endocrine neoplasia type-2 (MEN 2) syndromes are not novices to being pioneers in the modern era of (genetic) medicine: RET, along with the gsp (now GNAS) oncogene, were the first oncogenes to be found mutated in any genetic disorder predisposing to tumor formation (amazingly, both to endocrine tumors). The present volume is an extraordinary compilation of articles from some of the leading scientists and clinicians in the field of familial endocrine neoplasias, extending the field from the “classic” MENs, MEN 1 (8) and MEN 2 (9), to other syndromes predisposing to endocrine neoplasms among many other lesions, such as Carney complex (10), Von Hippel-Lindau disease (11), tumors associated with mutations of the succinate dehydrogenase enzyme (12), MEN 4 (13), and the neurofibromatosis and tuberous sclerosis syndromes (14). This presentation on MENs and MEN-related disorders is enhanced by an article on mouse models of endocrine tumors by Jones et al. (15). Finally, the last four articles of the volume present the significant advances in our understanding of the genetics of pituitary, adrenal, parathyroid and testicular (germ cell) tumors (16–19). One might ask why these four articles are included in a volume on “familial” endocrine neoplasias. The answer is clear: as we understand more about the genes that are involved in endocrine tumor formation, we find even more about genetic predisposition not only to the rare MENs and MEN-related syndromes, but also to common tumors. For example, a recent study found that as many as half of growth-hormone producing pituitary tumors in children and adolescents are caused by “mild” genetic defects in the germline, in genes such as AIP and menin (20). The clinician reader will find these articles a useful update on one of the most active areas of endocrinology, and one that is a leading field of translational Medicine. Researchers in the audience will find in this volume a guide to endocrine disease associated with aberrant signaling; understanding the complex interactions of genes that lead to endocrine tumors are essential for the current approach to cancer research, as well as for directing the development of molecularly designed drugs.