Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Calsina, Bruna
  • Piñeiro-Yáñez E
  • Martinez-Montes, Angel M.
  • Caleiras, Eduardo
  • Fernandez-Sanroman, Angel
  • Monteagudo, Maria
  • Torres-Perez, Rafael
  • Fustero-Torre, Coral
  • Pulgarin-Alfaro, Marta
  • Gil, Eduardo
  • Leton, Rocio
  • Jimenez, Scherezade
  • Garcia-Martin, Santiago
  • Martin, Maria Carmen
  • Roldan-Romero, Juan Maria
  • Lanillos, Javier
  • Mellid, Sara
  • Santos, Maria
  • Diaz-Talavera, Alberto
  • Rubio, Angeles
  • Gonzalez, Patricia
  • Hernando, Barbara
  • Bechmann, Nicole
  • Dona, Margo
  • Calatayud, Maria
  • Guadalix, Sonsoles
  • Alvarez-Escola, Cristina
  • Regojo, Rita M.
  • Aller, Javier
  • Lopez-Fernandez, Adria
  • Fliedner SMJ
  • Rapizzi, Elena
  • Fassnacht, Martin
  • Beuschlein, Felix
  • Quinkler, Marcus
  • Toledo, Rodrigo A.
  • Mannelli, Massimo
  • Timmers, Henri J.
  • Eisenhofer, Graeme
  • Rodriguez-Perales, Sandra
  • Dominguez, Orlando
  • Macintyre, Geoffrey
  • Curras-Freixes, Maria
  • Rodriguez-Antona, Cristina
  • Cascon, Alberto
  • Leandro-Garcia, Luis J.
  • Montero-Conde, Cristina
  • Roncador, Giovanna
  • Garcia-Garcia, Juan Fernando
  • Pacak, Karel
  • Al-Shahrour, Fatima
  • Robledo, Mercedes

Grupos

Abstract

The 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.

© 2023. The Author(s).

Datos de la publicación

ISSN/ISSNe:
2041-1723, 2041-1723

Nature Communications  NATURE PORTFOLIO

Tipo:
Article
Páginas:
1122-1122
PubMed:
36854674
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
4,846 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 69

Citas Recibidas en Scopus: 55

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Keywords

  • SOMATIC MUTATIONS; MICROSATELLITE INSTABILITY; COMPREHENSIVE ANALYSIS; RIBOSOME BIOGENESIS; TERT PROMOTER; CELL-CYCLE; CANCER; TUMORS; RNA; ACTIVATION

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