Mosaic Epigenetic Inheritance as a Cause of Early-Onset Colorectal Cancer.
JAMA Oncol
; 1(7): 953-7, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26181641
ABSTRACT
IMPORTANCE Constitutional hypermethylation of 1 allele throughout the soma (constitutional epimutation) is an accepted mechanism of cancer predisposition. Understanding the origin and inheritance of epimutations is important for assessing cancer risk in affected families. OBSERVATIONS We report a 29-year-old man with early-onset colorectal cancer who showed a constitutional MLH1 epimutation (approximately 50% of alleles methylated and allele-specific loss of MLH1 expression) that was stable over a 16-year period. The epimutation was inherited without a genetic alteration from his asymptomatic mother. She showed methylation on the same allele but in less than 5% of her somatic cells. CONCLUSIONS AND RELEVANCE These findings indicate that low-level somatic mosaicism for an epimutation in an asymptomatic parent can produce a nonmosaic constitutional epimutation in a child. Asymptomatic low-level methylation in some individuals may be associated with substantial cancer risk to their offspring.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Neoplasias Colorrectales
/
Adenocarcinoma
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Biomarcadores de Tumor
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Epigénesis Genética
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Proteínas Adaptadoras Transductoras de Señales
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Mosaicismo
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
JAMA Oncol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Australia