Pituitary adenoma comprise 10-15% of intracranial neoplasms and are amongst the commonest endocrine tumours. Tumour-associated mutations remain poorly understood. Germline mutations in Multiple Endocrine Neoplasia Type 1 and Aryl Carbon Interacting Protein cause a small proportion of pituitary tumours. However, it is thought most tumours are caused by sporadic mutations intrinsic to a single cell, supported by demonstration of monoclonality of pituitary tumours.
We aimed to understand the genetics of pituitary tumours. The components of the project were two-fold: establishment of a biobank including pituitary tumours; and use of pituitary tumour samples for whole exome sequencing (WES).
A polyuser CNS tumour bank was set up at the Wesley Medical Research labs with collection sites at multiple Brisbane hospitals. 14 pituitary tumours and paired blood samples were collected.
WES of 14 tumours and paired blood samples was performed, to identify somatic and germline mutations. 173 protein-altering somatic mutations were identified (mean of 12 mutations/tumour). Somatic GNAS mutations were identified in two somatotrophinomas. Somatic mutations in a novel gene were identified using sliding window and burden analysis.
We have established a tumour bank providing high quality samples for genetic studies. The identification of GNAS mutations in somatrotrophinomas is proof-of -concept. The discovery of a novel uncharacterized gene provides an opportunity for further identification of causes of pituitary tumourigenesis.