Landscape of genomic alterations in pituitary adenomas

Wenya Linda Bi, Peleg Horowitz, Noah F. Greenwald, Malak Abedalthagafi, Pankaj K. Agarwalla, Wiliam J. Gibson, Yu Mei, Steven E. Schumacher, Uri Ben-David, Aaron Chevalier, Scott Carter, Grace Tiao, Priscilla K. Brastianos, Azra H. Ligon, Matthew Ducar, Laura MacConaill, Edward R. Laws, Sandro Santagata, Rameen Beroukhim, Ian F. Dunn

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Pituitary adenomas are the second most common primary brain tumor, yet their genetic profiles are incompletely understood. Experimental Design: We performed whole-exome sequencing of 42 pituitary macroadenomas and matched normal DNA. These adenomas included hormonally active and inactive tumors, ones with typical or atypical histology, and ones that were primary or recurrent. Results: We identified mutations, insertions/deletions, and copy-number alterations. Nearly one-third of samples (29%) had chromosome arm-level copy-number alterations across large fractions of the genome. Despite such widespread genomic disruption, these tumors had few focal events, which is unusual among highly disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy number alterations involving less than 6% of the genome. Among the highly disrupted group, 75% were functional adenomas or atypical null-cell adenomas, whereas 87% of the less-disrupted group were nonfunctional adenomas. We confirmed this association between functional subtype and disruption in a validation dataset of 87 pituitary adenomas. Analysis of previously published expression data from an additional 50 adenomas showed that arm-level alterations significantly impacted transcript levels, and that the disrupted samples were characterized by expression changes associated with poor outcome in other cancers. Arm-level losses of chromosomes 1, 2, 11, and 18 were significantly recurrent. No significantly recurrent mutations were identified, suggesting no genes are altered by exonic mutations across large fractions of pituitary macroadenomas. Conclusions: These data indicate that sporadic pituitary adenomas have distinct copy-number profiles that associate with hormonal and histologic subtypes and influence gene expression.

Original languageEnglish
Pages (from-to)1841-1851
Number of pages11
JournalClinical Cancer Research
Volume23
Issue number7
DOIs
StatePublished - 1 Apr 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Landscape of genomic alterations in pituitary adenomas'. Together they form a unique fingerprint.

Cite this