학술논문
Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum.
Document Type
Article
Author
Fernández-Rozadilla, Ceres; Alvarez-Barona, Miriam; Schamschula, Esther; Bodo, Sahra; Lopez-Novo, Anael; Dacal, Andres; Calviño-Costas, Consuelo; Lancho, Angel; Amigo, Jorge; Bello, Xabier; Cameselle-Teijeiro, Jose Manuel; Carracedo, Angel; Colas, Chrystelle; Muleris, Martine; Wimmer, Katharina; Ruiz-Ponte, Clara
Source
Subject
*AGE factors in disease
*ALLELES
*DNA repair
*GENOMES
*METABOLIC disorders
*GENETIC mutation
*PHENOTYPES
*GENETIC testing
*HEREDITARY nonpolyposis colorectal cancer
*EARLY detection of cancer
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Language
ISSN
2072-6694
Abstract
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes. Biallelic mutations in these genes lead however, to constitutive mismatch repair deficiency (CMMRD). In this study, we follow the diagnostic journey of a 12-year old patient with CRC, with a clinical phenotype overlapping CMMRD. We perform molecular and functional assays to discard a CMMRD diagnosis then identify by exome sequencing and validation in a cohort of 134 LS patients, a candidate variant in the MLH1 UTR region in homozygosis. We propose that this variant, together with other candidates, could be responsible for age-of-onset modulation. Our data support the idea that low-risk modifier alleles may influence early development of cancer in LS leading to a LS-to-CMMRD phenotypic continuum. Therefore, it is essential that larger efforts are directed to the identification and study of these genetic modifiers, in order to provide optimal cancer prevention strategies to these patients. [ABSTRACT FROM AUTHOR]