Portal de investigación
MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Monteagudo M
- Calsina B
- Salazar-Hidalgo ME
- Martínez-Montes ÁM
- Piñeiro-Yáñez E
- Caleiras E
- Martín MC
- Rodríguez-Perales S
- Letón R
- Gil E
- Buffet A
- Burnichon N
- Fernández-Sanromán Á
- Díaz-Talavera A
- Mellid S
- Arroba E
- Reglero C
- Martínez-Puente N
- Roncador G
- Corrales PJP
- Oliveira CL
- Álvarez-Escolá C
- Gutiérrez MC
- López-Fernández A
- García NP
- Regojo RM
- Díaz LR
- Laorden NR
- Guadarrama OS
- Bechmann N
- Beuschlein F
- Canu L
- Eisenhofer G
- Fassnacht M
- Nölting S
- Quinkler M
- Rapizzi E
- Remde H
- Timmers HJ
- Favier J
- Gimenez-Roqueplo AP
- Rodriguez-Antona C
- Currás-Freixes M
- Al-Shahrour F
- Cascón A
- Leandro-García LJ
- Montero-Conde C
- Robledo M
Grupos
Abstract
Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 1521-690X, 1532-1908
- Tipo:
- Article
- Páginas:
- 101931-101931
- PubMed:
- 39218714
- Factor de Impacto:
- 1,166 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM ELSEVIER SCI LTD
Citas Recibidas en Web of Science: 7
Documentos
- No hay documentos
Filiaciones
Keywords
- MAML3 screening procedure; MAML3-fusion; metastasis; paraganglioma; pheochromocytoma; tumour microenvironment; vasculature
Cita
Monteagudo M,Calsina B,Salazar ME,Martínez ÁM,Piñeiro E,Caleiras E,Martín MC,Rodríguez S,Letón R,Gil E,Buffet A,Burnichon N,Fernández Á,Díaz A,Mellid S,Arroba E,Reglero C,Martínez N,Roncador G,DEL OLMO MI,Corrales PJP,Oliveira CL,Álvarez C,Gutiérrez MC,López A,García NP,Regojo RM,Díaz LR,Laorden NR,Guadarrama OS,Bechmann N,Beuschlein F,Canu L,Eisenhofer G,Fassnacht M,Nölting S,Quinkler M,Rapizzi E,Remde H,Timmers HJ,Favier J,Gimenez AP,Rodriguez C,Currás M,Al F,Cascón A,Leandro LJ,Montero C,Robledo M. MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma. Best Pract. Res. Clin. Endoc. Metab. 2024. 38. (6):p. 101931-101931. IF:6,100. (1).