Endocrine Abstracts

Background: Pituitary adenomas are the most common intracranial neoplasm, with a slow-growing, locally invasive phenotype. Some result from syndromes or isolated germ-line mutations, while approximately 60% have no currently identified somatic mutation implicated in tumorigenesis. High throughput technologies such as microarray, RNA sequencing (RNAseq) and next-generation sequencing (NGS, incorporating whole genome- and exome sequencing) have recently been used to identify altered genes and pathways involved in tumorigenesis.

Aims: To perform a comparative analysis and literature review of microarray, RNAseq and NGS studies into human pituitary tumours.

Methods: Ovid MEDLINE and EMBASE databases were searched in a systematic method (to May 2019) and relevant papers selected. Included papers assessed human pituitary adenomas of any hormonal profile using high throughput sequencing technology. Targeted approaches, previously identified somatic mutations, and non-coding RNA studies were excluded. 35 papers were reviewed in total.

Results: One new recurring somatic mutation in corticotrophomas, USP8, was identified using whole exome sequencing. One previously identified mutation in somatotrophinomas, GNAS, was also noted. Key pathways were noted as differentially enriched, including Wnt and Notch signalling, epithelial mesenchymal transition (EMT) and extracellular matrix adhesion (ECM). Microarray technology is the most common high throughput technology in use, with NGS and RNAseq in use for the last six years.

Conclusion: High throughput technologies have developed recently, with whole exome and genome sequencing becoming more ubiquitous. These technologies may be more useful for identifying differentially enriched pathways than for singular recurrent somatic mutations. The pathways identified have clear roles in tumorigenesis and pituitary development and are potential targets for novel therapeutic agents and further research. Future research may assess the findings of non-coding RNA studies.