A germline mutation in PBRM1 predisposes to renal cell carcinoma.
J Med Genet
; 52(6): 426-30, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-25911086
ABSTRACT
BACKGROUND:
Many cases of familial renal cell carcinoma (RCC) remain unexplained by mutations in the known predisposing genes or shared environmental factors. There are therefore additional, still unidentified genes involved in familial RCC. PBRM1 is a tumour suppressor gene and somatic mutations are found in 30-45% of sporadic clear cell (cc) RCC.METHODS:
We selected 35 unrelated patients with unexplained personal history of ccRCC and at least one affected first-degree relative, and sequenced the PBRM1 gene.RESULTS:
A germline frameshift mutation (c.3998_4005del [p.Asp1333Glyfs]) was found in one patient. The patient's mother, his sister and one niece also had ccRCC. The mutation co-segregated with the disease as the three affected relatives were carriers, while an unaffected sister was not, according with autosomal-dominant transmission. Somatic studies supported these findings, as we observed both loss of heterozygosity for the mutation and loss of protein expression in renal tumours.CONCLUSIONS:
We show for the first time that an inherited mutation in PBRM1 predisposes to RCC. International studies are necessary to estimate the contribution of PBRM1 to RCC susceptibility, estimate penetrance and then integrate the gene into routine clinical practice.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas Nucleares
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Carcinoma de Células Renales
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Mutación de Línea Germinal
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Predisposición Genética a la Enfermedad
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Neoplasias Renales
Tipo de estudio:
Diagnostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Año:
2015
Tipo del documento:
Article