Dipika R Mohan, Ticiana Paes, Jacobo Buelvas Mebarak, David M Meredith, Beatriz Soares, Victor Vaz, Rona S Carroll, Ursula B Kaiser, Timothy R Smith, Wenya L Bi, Antonio M Lerario, Ana Paula Abreu
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引用次数: 0
Abstract
Objective: Pituitary adenomas (PAs) are common neoplasms. Our current understanding of the molecular basis of PA formation is incomplete. Routine implementation of targeted genomics has enabled the discovery of rare, potentially clinically actionable events.
Methods: We used a cancer-focused gene panel to sequence a cohort of 171 PAs from patients who underwent surgery at Brigham and Women's Hospital from 2012 to 2020.
Results: We identified known genetic variants enriched in specific PA subtypes: GNAS (somatotroph) and USP8 (Cushing's disease). Total mutational burden did not vary across adenoma subtypes; most adenomas possessed a few non-recurrent mutations in various established oncogenes and tumor suppressors. In contrast, the burden of copy number alterations varied widely across adenoma subtypes and was associated with higher MIB1 labeling index. We identified frequent deletions spanning MEN1 in prolactinomas and silent corticotroph adenomas, and subtype-specific copy number changes including 16p, 16q alterations in somatotroph adenomas without GNAS mutations. Within the corticotroph lineage, adenomas leading to Cushing's disease had few copy number alterations while silent corticotroph adenomas had numerous.
Conclusions: This study highlights a role for individualized genetic events in PA formation and suggests that divergent patterns of genomic instability may facilitate tumorigenesis even within the same lineage. Taken together, we demonstrate how gene panels may illuminate novel biology in endocrine tumors.
期刊介绍:
European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica.
The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology.
Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials.
Equal consideration is given to all manuscripts in English from any country.