USP8 and TP53 drivers are associated with CNV in a corticotroph adenoma cohort enriched for aggressive tumors

Context: Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropic hormone (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown.

Objective: To investigate genomic drivers of corticotroph tumors at risk for aggressive behavior.

Design: Whole-exome sequencing of patient-matched corticotroph tumor and normal DNA from a patient cohort enriched for tumors at risk for aggressive behavior.

Setting: Tertiary care center.

Patients: 27 corticotroph tumors from 22 patients analyzed. 12 tumors were macroadenomas, of which 6 were silent ACTH tumors, 2 were Crooke’s cell tumors, and 1 was a corticotroph carcinoma.

Intervention: Whole-exome sequencing.

Main outcome measure: Somatic mutation genomic biomarkers.

Results: We found recurrent somat...