Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment.

Autor: Zethoven M; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Martelotto L; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Pattison A; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Bowen B; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Balachander S; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Flynn A; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Rossello FJ; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Hogg A; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Miller JA; Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia.; Department of Surgery, Epworth Hospital, Richmond, VIC, Australia., Frysak Z; 3rd Department of Internal Medicine - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic., Grimmond S; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia., Fishbein L; Department of Medicine, Division of Endocrinology, Metabolism, Diabetes, University of Colorado, Aurora, CO, USA., Tischler AS; Tufts Medical Centre, Boston, MA, USA., Gill AJ; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.; Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia.; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia., Hicks RJ; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Dahia PLM; Div. Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA., Clifton-Bligh R; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.; Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia., Pacak K; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA., Tothill RW; Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia. rtothill@unimelb.edu.au.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. rtothill@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 21; Vol. 13 (1), pp. 6262. Date of Electronic Publication: 2022 Oct 21.
DOI: 10.1038/s41467-022-34011-3
Abstrakt: Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.
(© 2022. The Author(s).)
Databáze: MEDLINE
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