Non-recurrent mutations and copy number changes predominate pituitary adenoma genomes

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Pituitary adenomas (PAs) are common tumors, but their molecular origins remain incompletely understood.
• Targeted genomic analysis is increasingly identifying clinically relevant genetic events in PAs.

Purpose of the Study:

• To investigate the genetic landscape of pituitary adenomas using a comprehensive gene panel.
• To identify novel molecular drivers and patterns of genomic instability in different PA subtypes.

Main Methods:

• Sequencing of 171 pituitary adenomas using a cancer-focused gene panel.
• Analysis of genetic variants, mutational burden, and copy number alterations across PA subtypes.

Main Results:

• Identified known variants (GNAS, USP8) specific to somatotroph and Cushing's disease adenomas.
• Found varying copy number alterations across subtypes, linked to MIB1 index; frequent MEN1 deletions in prolactinomas.
• Observed distinct genomic profiles in corticotroph adenomas, with silent types showing more alterations than those causing Cushing's disease.

Conclusions:

• Individualized genetic events play a role in pituitary adenoma development.
• Divergent genomic instability patterns contribute to tumorigenesis, even within the same cell lineage.
• Gene panels are valuable tools for uncovering new biological insights in endocrine tumors.