Dataset Information

Landscape of Genomic Alterations in Pituitary Adenomas.

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. Clin Cancer Res; 23(7); 1841-51. ©2016 AACR.

SUBMITTER: Bi WL

PROVIDER: S-EPMC5380512 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Landscape of Genomic Alterations in Pituitary Adenomas.

Bi Wenya Linda WL Horowitz Peleg P Greenwald Noah F NF Abedalthagafi Malak M Agarwalla Pankaj K PK Gibson Wiliam J WJ Mei Yu Y Schumacher Steven E SE Ben-David Uri U Chevalier Aaron A Carter Scott S Tiao Grace G Brastianos Priscilla K PK Ligon Azra H AH Ducar Matthew M MacConaill Laura L Laws Edward R ER Santagata Sandro S Beroukhim Rameen R Dunn Ian F IF

Clinical cancer research : an official journal of the American Association for Cancer Research 20161005 7

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 o ...[more]

PMID: 27707790

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Dataset Information

Landscape of Genomic Alterations in Pituitary Adenomas.

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Landscape of Genomic Alterations in Pituitary Adenomas.

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