Genomics of Pituitary Adenomas

Pituitary adenomas (PA) are common intracranial tumors with heterogeneous clinical behavior, ranging from indolent lesions to invasive, treatment resistant disease. Although the majority of these tumors are sporadic, a significant proportion has a genetic basis. The genetically-based PA may occur as part of familial syndromes (e.g. MEN1, Carney complex) or manifest as apparently sporadic but show genetic alterations upon genetic testing.

Many underlying genes have been discovered in the last few years including AIP, MEN1, CDKN1B, SDHx, and CDH23. Some of these genes causes known syndromes (e.g. MEN1, DICER1, SDHx) while others manifest usually with PA alone (e.g. AIP). Over the last decade, it has become clear that the role of genetics in PA is expanding. Reliable genomic indicators for disease aggressiveness and treatment response and long-term outcomes remain scarce thus the need for robust biomarkers and integrated molecular models. Furthermore, despite existing knowledge, the field of molecular genetics of PA has yet to be fully translated to clinical practice.

In this study, we plan to comprehensively characterize the underlying genetics of PA in Saudi Arabia and study these tumors at germline and somatic levels to define the genotype-phenotype relationship and the genetic signatures associated with aggressive behavior and resistance to therapy.

Expected outcomes: (i) Identify the prevalence of germline genetic alterations in PA. (ii) Potential discovery of new genes causing PA. (iii) define genotype-phenotype relationships and build internally validated predictive models for disease aggressiveness and treatment effectiveness. (iv) The study will offer healthcare providers a clinical decision support for genetic evaluation and monitoring programs which enable personalized endocrinology practice in PA patients.

The project aligns with the Health Sector Transformation through precision medicine capabilities and is in alignment with vision 2030 of advancing cancer care in Saudi Arabia.