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Somatic Genetic Alterations in Pituitary Neuroendocrine Tumors
Yair Schwarz1,2, Reut Halperin3,4, Amit Tirosh3,4
1Clinical Center for Pituitary Diseases, Division of Endocrinology, Metabolism, and Diabetes, Sheba Medical Center , Ramat Gan, Israel.
Endocrine-Related Cancer
|August 7, 2026
Summary
Recent advances in pituitary neuroendocrine tumor (PitNET) molecular characterization reveal key driver alterations in specific PitNET types. These findings are paving the way for improved classification and targeted therapies.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Pituitary neuroendocrine tumors (PitNETs) classification is evolving with molecular insights.
- Understanding PitNET biology requires detailed characterization of genetic and epigenetic drivers.
Purpose of the Study:
- To provide a comprehensive update on molecular alterations in PitNETs.
- To integrate multi-omics data for improved PitNET classification and identify therapeutic targets.
Main Methods:
- Review of published cohort analyses.
- Integration of genomic, transcriptomic, epigenomic, and proteomic data.
- Analysis of somatic driver alterations and epigenetic modifications.
Main Results:
- Identified frequent somatic driver alterations in corticotroph (USP8, USP48, BRAF), somatotroph (GNAS), and lactotroph (SF3B1) PitNETs.
- Enrichment of TP53, ATRX, and DAXX in aggressive corticotroph tumors.
- Emerging role of epigenetic modifications (DNA methylation, histone modifications, non-coding RNAs) in PitNET pathogenesis.
Conclusions:
- Molecular profiling enables refined PitNET subclassification and earlier identification of aggressive variants.
- Identified molecular markers offer potential for novel targeted therapies.
- Multi-omics approaches are transforming PitNET classification and therapeutic strategies.
