Abstract
Background:
The genetic underpinnings of sporadic pituitary adenomas remain incompletely understood, despite their prevalence. We characterized the genetic signatures of 42 pituitary macroadenomas, including hormonally active and atypical adenomas.
Methods:
Pituitary adenomas representative of a spectrum of histopathologic subtypes, de novo and recurrent tumors, and MIB-1 proliferative indices were profiled. Whole-exome sequencing was performed on tumor and paired blood to identify somatic copy-number alterations, mutations, insertions and deletions.
Results:
Pituitary tumors stratified into two classes based upon the fraction of their genome disrupted. One class (71% of tumors) had somatic copy-number alterations involving less than 6% of the genome; the other class (29%) had significantly greater levels of genomic disruption, with up to 99% of the genome involved. The widespread genomic disruption observed in the second class was largely accounted for by arm-level events, with minimal involvement of focal events, which is rare among cancers. Levels of genomic disruption were associated with phenotype. Among the less disrupted group, 87% (26/30) were clinically non-functional adenomas, whereas the majority of the disrupted group were functional or atypical null-cell adenomas. The high and low genomic disruption classes did not differ in mean MIB-1 proliferative index. Frequent loss of chromosomes 11 and 1p were observed, as well as significant recurrent amplifications of chromosome 5, 7, 9, 12, and 14q. On the whole, the tumors harbored a low rate of mutations, similar to other benign brain tumors.
Conclusions:
Genomic characterization of a large series of sporadic pituitary adenomas reveals two distinct classes of tumor, based on genomic disruption from broad copy-number alterations, and associates with tumor subtype.