The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma
| Autor: | Jasper Wu, Daniel Phillips, Elizabeth C Treynor, Jeffrey W. Hofmann, Susan M Bator, Emily A. Sloan, Praveen V. Mummaneni, Rohit Gupta, Jairo Barreto, Arie Perry, Nancy Ann Oberheim Bush, Daniel V Sullivan, Andrew W. Bollen, Biswarathan Ramani, Mitchel S. Berger, Susan M. Chang, Tarik Tihan, Viktor Zherebitskiy, Paula S Quinn, Nicholas Butowski, Jeffrey B Walker, Melike Pekmezci, Aaron J. Clark, Bruce E King, Christopher P. Ames, David A. Solomon |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Pathology Cauda Equina SDHB Neuroendocrine tumors Metastasis Central Nervous System Neoplasms 0302 clinical medicine 80 and over Spinal Paraganglioma Aged 80 and over Cauda equina paraganglioma Cauda equina Middle Aged Immunohistochemistry Succinate dehydrogenase medicine.anatomical_structure DNA methylation DNA methylation profiling Female Adult medicine.medical_specialty DNA Copy Number Variations Molecular neuropathology Clinical Sciences Copy number analysis Biology Article Pathology and Forensic Medicine Paraganglioma 03 medical and health sciences Cellular and Molecular Neuroscience Young Adult Germline mutation Neuroendocrine tumor Clinical Research medicine Genetics Humans Germ-Line Mutation Aged Neurology & Neurosurgery Filum terminale Human Genome Neurosciences DNA Methylation medicine.disease 030104 developmental biology Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Acta neuropathologica, vol 140, iss 6 Acta Neuropathol |
| Popis: | Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated seventeen CEPs from eleven male and six female patients with a median age of 38 years (range 21–82), none with a family history of neuroendocrine neoplasia. Six of the seventeen tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all seventeen CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on twelve of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|