Evidence of predisposing epimutation in retinoblastoma.
Hum Mutat
; 40(2): 201-206, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30427563
ABSTRACT
Retinoblastoma (RB), which represents the most common childhood eye cancer, is caused by biallelic inactivation of RB1 gene. Promoter hypermethylation is quite frequent in RB tissues but conclusive evidence of soma-wide predisposing epimutations is currently scant. Here, 50 patients who tested negative for RB1 germline sequence alterations were screened for aberrant promoter methylation using methylation-specific MLPA. The assay, performed on blood, identified a sporadic patient with methylation of CpG106, absent in parents' DNA. Bisulfite pyrosequencing accurately quantified CpG methylation in blood DNA (mean â¼49%) and also confirmed the aberration in DNA isolated from oral mucosa although at lower levels (mean â¼34%). Using a tag-SNP, methylation was demonstrated to affect the maternal allele. Real-time qPCR demonstrated RB1 transcriptional silencing. In conclusion, we documented that promoter methylation can act as the first "hit" in Knudson's model. This mosaic epimutation mimics the effect of an inactivating mutation and phenocopies RB onset.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinoblastoma
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Metilação de DNA
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Predisposição Genética para Doença
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Ubiquitina-Proteína Ligases
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Proteínas de Ligação a Retinoblastoma
Limite:
Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article