Portal de investigación
DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients
Autores organización
Autores
- Chamorro Ortiz DF
- Ruíz-Patiño A
- Gomez D
- Muñoz Á
- Ardila DV
- Garcia-Robledo JE
- Ordóñez-Reyes C
- Sussmann L
- Mosquera A
- Forero Y
- Hakim F
- Jimenez E
- Ramón JF
- Cifuentes H
- Pineda D
- Mejía JA
- Rodríguez J
- Archila P
- Sotelo C
- Moreno-Pérez DA
- Arrieta O
Grupos de investigación
Resumen
Background: DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary DICER1-associated CNS sarcoma"(DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods: We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results: Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions: DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways. © 2023 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved.
© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Datos de la publicación
- ISSN/ISSNe:
- 2054-2577, 2054-2585
- Tipo:
- Article
- Páginas:
- 381-390
- DOI:
- 10.1093/nop/npad014
- Enlace a otro recurso:
- www.scopus.com
Neuro-Oncology Practice Oxford University Press
Citas Recibidas en Scopus: 8
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Filiaciones
Keywords
- cisplatin; etoposide; ifosfamide; ribonuclease III; adult; Article; brain tumor; cancer growth; cancer survival; case study; central nervous system sarcoma; chemoradiotherapy; chondrosarcoma; clinical article; clinical outcome; DICER1 syndrome; female; gene mutation; high throughput sequencing; histology; histopathology; human; human tissue; immunohistochemistry; liquid biopsy; male; MAPK signaling; multicenter study; overall survival; Pi3K/Akt signaling; progression free survival; retrospective study; sarcoma; sequence analysis; spindle cell sarcoma; treatment response time; tumor mutational burden; young adult
Proyectos asociados
Citar la publicación
Cardona AF,Chamorro DF,Ruíz A,Gomez D,Muñoz Á,Ardila DV,Garcia JE,Ordóñez C,Sussmann L,Mosquera A,Forero Y,Rojas L,Hakim F,Jimenez E,Ramón JF,Cifuentes H,Pineda D,Mejía JA,Rodríguez J,Archila P,Sotelo C,Moreno DA,Arrieta O. DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients. Neurooncol Pract. 2023. 10. (4):p. 381-390.