Molecular and cellular pathogenesis of pituitary tumors

Abstract

Pituitary tumors occur sporadically (95%) or as hereditary tumors, either associated with endocrine syndromes (2.5%) or as familial isolated variants (FIPA, 2.5%). In sporadic pituitary tumors, in addition to the known somatotropic GNAS mutation, a recurrent mutation of the USP8 gene was recently detected in corticotropinomas. Thus variable genetic and epigenetic modifications may mostly be responsible for pituitary tumorigenesis. However, these different changes seem to modify common intracellular targets such as distinct tumor suppressors, cell cycle checkpoints or signaling pathways. Thus, recurrently impaired functions in concert with/or recurrently impaired genes may trigger pituitary tumorigenesis. This may also be of relevance for the different steps involved in pituitary tumor progression such as angiogenesis, invasiveness, pituitary tumor senescence and pituitary carcinoma formation.