Pituitary tumours: molecular and genetic aspects

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Pituitary adenomas are common tumours of the hypothalamic-pituitary system, affecting approximately 1 in 1000 individuals.
• While most pituitary tumours are adenomas, rare types like craniopharyngioma and pituicytoma also exist.
• This review focuses on the molecular and genetic underpinnings of pituitary adenomas.

Approach:

• Examines germline genetic variants associated with familial pituitary tumours, including mutations in MEN1, PRKAR1A, AIP, and SDH genes.
• Discusses McCune-Albright syndrome, characterized by postzygotic GNAS mutations, and its association with multiglandular features.
• Reviews somatic genetic and molecular alterations in sporadic pituitary adenomas, such as copy number variations and pathway dysregulation.

Key Points:

• Germline variants in specific genes predispose individuals to pituitary adenomas, accounting for about 5% of cases.
• Somatic GNAS mutations are implicated in sporadic acromegaly, and USP8 mutations are identified in other sporadic pituitary tumours.
• A wide range of somatic changes, including signalling pathway alterations, DNA repair defects, and epigenetic modifications, contribute to sporadic pituitary adenoma development.

Conclusions:

• Genetic factors play a significant role in both familial and sporadic pituitary adenoma development.
• Further research into the molecular landscape of pituitary tumours can lead to improved diagnostic and therapeutic strategies.
• Understanding the genetic basis of pituitary tumours is essential for advancing personalized medicine approaches.