Evidence of predisposing epimutation in retinoblastoma.

Alleles DNA Methylation / genetics Epigenesis, Genetic Female Gene Silencing Genetic Predisposition to Disease Humans Infant Male Mutation / genetics Polymorphism, Single Nucleotide / genetics Promoter Regions, Genetic Retinoblastoma / genetics Retinoblastoma Binding Proteins / genetics Ubiquitin-Protein Ligases / genetics
epimutation gene silencing mosaicism promoter methylation retinoblastoma

Journal

Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429

Informations de publication

Date de publication:
02 2019
Historique:
received: 24 05 2018
revised: 04 10 2018
accepted: 12 11 2018
pubmed: 15 11 2018
medline: 10 3 2020
entrez: 15 11 2018
Statut: ppublish

Résumé

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 ∼49%) and also confirmed the aberration in DNA isolated from oral mucosa although at lower levels (mean ∼34%). 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.

Identifiants

DOI: 10.1002/humu.23684 PMID: 30427563
pubmed: 30427563
doi: 10.1002/humu.23684
doi:

Substances chimiques

RB1 protein, human 0
Retinoblastoma Binding Proteins 0
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

201-206

Informations de copyright

© 2018 Wiley Periodicals, Inc.

Auteurs

Elisa Gelli (E)

Medical Genetics, University of Siena, Siena, Italy.

Anna Maria Pinto (AM)

Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Serena Somma (S)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Valentina Imperatore (V)

Medical Genetics, University of Siena, Siena, Italy.

Marta G Cannone (MG)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Theodora Hadjistilianou (T)

Unit of Ophthalmology and Retinoblastoma Referral Center, Department of Surgery, University of Siena, Policlinico 'Santa Maria alle Scotte', Siena, Italy.

Sonia De Francesco (S)

Unit of Ophthalmology and Retinoblastoma Referral Center, Department of Surgery, University of Siena, Policlinico 'Santa Maria alle Scotte', Siena, Italy.

Daniela Galimberti (D)

Unit of Pediatrics, Department of Maternal, Newborn and Child Health, Azienda Ospedaliera Universitaria Senese, Policlinico 'Santa Maria alle Scotte', Siena, Italy.

Aurora Currò (A)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Mirella Bruttini (M)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Francesca Mari (F)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Alessandra Renieri (A)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
ORCID: 0000-0002-0846-9220

Francesca Ariani (F)

Medical Genetics, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Tumeurs de la rétine › Rétinoblastome › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines de liaison à la protéine du rétinoblastome › Evidence of predisposing epimutation in retinoblastoma.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Evidence of predisposing epimutation in retinoblastoma.