Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma

descriptionPublicationkeyboard_double_arrow_right Article 28 Feb 2023 Spain, Netherlands, Italy English Publisher:Springer Science and Business Media LLCJournal:Nature Communications, volume 14 (eissn: 2041-1723,

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Authors: Bruna Calsina; Elena Piñeiro-Yáñez; Ángel M. Martínez-Montes; Eduardo Caleiras; Ángel Fernández-Sanromán; María Monteagudo; Rafael Torres-Pérez; +46 Authors

Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma

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Abstract

AbstractThe mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.

Countries

Spain, Netherlands, Italy

Related Organizations

University of Zurich
Switzerland
TU Dresden
Germany
Vall d'Hebron Institute of Oncology (VHIO)
Spain
University of Florence
Italy
Hospital Universitario 12 De Octubre
Spain

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Keywords

TERT PROMOTER, MICROSATELLITE INSTABILITY, Science, Adrenal Gland Neoplasms, Radboud University Medical Center, Pheochromocytoma, COMPREHENSIVE ANALYSIS, Article, ACTIVATION, Paraganglioma, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::paraganglioma, Metàstasi, Tumor Microenvironment, CELL-CYCLE, Humans, Radboudumc 16: Vascular damage Internal Medicine, RIBOSOME BIOGENESIS, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral, Genomic and immune landscape, metastatic pheochromocytoma and paraganglioma, Q, DISCIPLINAS Y OCUPACIONES::disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::biología::biología computacional::genómica, Neoplasms, Second Primary, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Paraganglioma, SOMATIC MUTATIONS, Genomics, CANCER, TUMORS, Genòmica, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Paraganglioma::Pheochromocytoma, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment, RNA, DISCIPLINES AND OCCUPATIONS::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology::Genomics, Tumors neuroendocrins - Aspectes genètics, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::paraganglioma::feocromocitoma

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