Genetic background of MEN1: from genetic homogeneity to functional diversity

Multiple Endocrine Neoplasia Type 1 corresponds to a monogenic predisposition syndrome inherited as a dominant trait that affects a variety of endocrine tissues, in particular parathyroids, endocrine pancreas and anterior pituitary. It is caused by mutations in the MEN1 tumor suppressor gene that inactivate menin, the MEN1 encoded protein. Menin is involved in cell cycle control and apoptosis through its participation in functional dynamics of chromatin and regulation of transcription. In addition, genetic investigations have implicated menin in the maintenance of genomic integrity. However, the role of menin does not--by far--end here. It plays (too) many roles in the control of cell life and normality, far beyond endocrine oncogenesis, making it unlikely that the function of menin can be deciphered only by genetic investigation. In this context, writing a chapter on the genetic background of MEN1 appears at the same time as a challenge and a paradox. A challenge as everything has been either already written on the topic or included in the present book. A paradox since genetics is simultaneously at the background and at the forefront of MEN1. Our attempts are thus more investigating new--as well as already open issues than delivering a catalog of MEN1 gene mutations.