Abstract

Adamantinomatous craniopharyngioma (ACP) are clinically relevant tumours that are associated with high morbidity, poor quality of life and occasional mortality. Human and mouse studies have provided important insights into the biology of these aggressive tumours and we are starting to understand why, how and when these tumours develop in humans. Mutations in β-catenin resulting in the over-activation of the WNT/β-catenin signalling pathway are critical drivers of most, perhaps of all, human ACPs. Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumours when targeted with oncogenic β-catenin, suggesting that the cell context is critical for mutant β-catenin to exert its oncogenic effect. Interestingly, mutant stem cells do not generate the bulk of the tumour cells, instead they induce tumours in a paracrine manner. Combining basic studies in mice and humans will provide further insights into the biology of these neoplasms, revealing pathogenic pathways that could be targeted with specific inhibitors for the benefit of the patients. These benign tumours may additionally represent a unique model to investigate the early steps leading to oncogenesis.