Integrative clinical and molecular characterization of translocation renal cell carcinoma.
Cell Rep
; 38(1): 110190, 2022 01 04.
Article
em En
| MEDLINE
| ID: mdl-34986355
ABSTRACT
Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) are worse than those treated with immune checkpoint inhibitors (ICI). Using multiparametric immunofluorescence, we find that the tumors are infiltrated with CD8+ T cells, though the T cells harbor an exhaustion immunophenotype distinct from that of clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Proteínas de Fusão Oncogênica
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Fator de Transcrição Associado à Microftalmia
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Neoplasias Renais
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos