Micro-RNA Mutations Across Multiple Resections of a Giant Nonfunctional Pituitary Adenoma

Introduction: Nonfunctional pituitary adenomas are one of the most common types of brain tumors, but the landscape of genomic alterations is not well understood. Despite widespread genetic disruptions in pituitary adenomas, they are known to harbor few focal events. Increasingly, epigenetic factors are thought to play a role in pituitary adenoma tumorigenesis. MicroRNAs are noncoding RNAs that modulate posttranscriptional gene expression by affecting stability and translation of messenger RNAs, thought to control 30–50% of protein-coding genes. A variety of miRNAs have been previously implicated in functional and nonfunctional microRNAs but has never been shown to be preserved during tumor development.

Methods: High throughput sequencing was performed to analyze a giant pituitary adenoma specimen for somatic mutations in three different time points.

Results: We present a 41-year-old patient who presented with headache and 2 months of visual changes and galactorrhea, found to have 3.7 cm × 5.2 cm pituitary giant adenoma. Patient underwent three staged operations using different approaches and whole-exome sequenced at a different site with each resection, over a 13-month period. She initially had a right supraorbital craniotomy, followed by endoscopic endonasal transsphenoidal approach, and lastly an endoscopic endonasal trans-planum approach. Her headaches and visual impairment improved after treatment.

The first sample had a growth hormone secretagogue receptor mutation, and all three samples of tissue had a conserved mutation in microRNA MIR1268A. Prior studies have not identified this microRNA involved in pituitary adenomas.

Conclusions: This case serves as a novel example of a pituitary adenoma biopsied at several time points at different locations. All samples show a similar somatic mutation burden with only a single conserved miRNA mutation and similar somatic copy number profiles pointing to intratumoral genetic homogeneity.