Portal de investigación
Primary constitutional MLH1 epimutations: a focal epigenetic event
Fecha de publicación:
Autores de FISABIO
Autores ajenos a FISABIO
- del Mar Arias, Maria
- Canet-Hermida, Julia
- Navarro, Matilde
- del Valle, Jesus
- Campos, Olga
- Fernandez, Anna
- Marin, Fatima
- Turchetti, Daniela
- de Dios Garcia-Diaz, Juan
- Lazaro, Conxi
- Genuardi, Maurizio
- Rueda, Daniel
- Alonso, Angel
- Hitchins, Megan
- Pineda, Marta
- Capella, Gabriel
Grupos de Investigación
Abstract
BACKGROUND: Constitutional MLH1 epimutations are characterised by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterisation of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci. METHODS: Twelve MLH1 epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were analysed by Infinium 450 K array. Targeted molecular techniques were used to characterise the MLH1 epimutation carriers and their inheritance pattern. RESULTS: No nucleotide or structural variants were identified in-cis on the epimutated allele in 10 carriers, in which inter-generational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls. CONCLUSION: Primary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP7-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterisation is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility.
Datos de la publicación
- ISSN/ISSNe:
- 0007-0920, 1532-1827
- Tipo:
- Article
- Páginas:
- 978-987
- PubMed:
- 30283143
BRITISH JOURNAL OF CANCER SPRINGERNATURE
Citas Recibidas en Web of Science: 26
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