Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors.
Cancer Genet
; 258-259: 51-56, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34488032
ABSTRACT
Hereditary Renal Cell Carcinomas (RCC) are caused by mutations in predisposing genes, the major ones including VHL, FLCN, FH and MET. However, many families with inherited RCC have no germline mutation in these genes. Using Whole Exome Sequencing on germline DNA from a family presenting three different histological renal tumors (an angiomyolipoma, a clear-cell RCC and an oncocytic papillary RCC), we identified a frameshift mutation in the Neighbor of BRCA1 gene 1 (NBR1), segregating with the tumors. NBR1 encodes a cargo receptor protein involved in autophagy. Genetic and functional analyses suggested a pathogenic impact of the mutation. Indeed, functional study performed in renal cell lines showed that the mutation alters NBR1 interactions with some of its partners (such as p62/SQSTM1), leading to a dominant negative effect. This results in an altered autophagic process and an increased proliferative capacity in renal cell lines. Our study suggests that NBR1 may be a new predisposing gene for RCC, however its characterization needs to be further investigated in order to confirm its role in renal carcinogenesis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Carcinoma de Células Renais
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Mutação em Linhagem Germinativa
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Predisposição Genética para Doença
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Peptídeos e Proteínas de Sinalização Intracelular
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Neoplasias Renais
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Genet
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França