Applications of genomic medicine in endocrinology and post-genomic endocrine research

Abstract

In the mid 1980s, two advances revolutionized Medicine in a way that is comparable only to some of the most important events in the approximately 3,000 years of its history. The first was the introduction of the concept of positional cloning, i.e. the idea that one can identify genes for human disease though knowing nothing or very little about their function. The second was the discovery of the method of polymerase chain reaction (PCR) which made DNA easier to work with for all biomedical researchers and clinicians. Fresh in the history of Endocrinology were the great discoveries of neuroendocrinology, and even more contemporary and potent, the influence of the then emerging field of molecular endocrinology. Cancer medicine and traditional human genetics were the fields that benefited most from the first applications of the new genomic concepts and technologies. Almost two decades later, and after the first successful applications of positional cloning in Endocrine Genetics with the identification of RET, menin, PTEN and PRKAR1A in the various forms of multiple endocrine tumor syndromes, and a number of other genes in developmental diseases affecting the pituitary, thyroid, parathyroid, pancreas, adrenal and gonadal glands, endocrinology has made a comeback to the forefront of genomically-influenced as well as post-genomic Medicine. This report, using the example of endocrine tumor genetics, presents the process and some of the accomplishments of positional cloning and discusses the influence of endocrinology on contemporary translational research. The author suggests that some of the most traditional endocrine concepts, established in the previous two centuries, could help us understand the complex pathways recently unraveled in cancer genetics and, consequently, other fields. It is suggested that Endocrine genes that control cellular signaling act as conductors since they regulate differentiation, growth and proliferation. Their complex function and resultant transcriptomes are now being investigated by post-genomic Medicine. In cancer research, endocrine genes defy classic definitions of tumor suppressors and oncogenes and regulate gatekeepers, caretakers, and landscapers. In the post-genomic, translational Medicine, Endocrinology once again could help us to understand cellular regulation and pathophysiology and to design new treatments.

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

“…Genetic and molecular alterations have been the subject of several studies, without, however, definitive conclusions being reached (Stratakis 2003, 2005, Lombardi et al 2006. 1 H-high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy can characterize the metabolic phenotype of intact cells, tissues, and organs from the analysis of an intact tissue sample (Nicholson & Wilson 2003).…”