RT Journal Article
T1 Early colorectal cancers provide new evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
A1 Fernández Rozadilla, Ceres
A1 Álvarez Barona, Miriam
A1 Schamschula, Esther
A1 Bodo, Sahra
A1 López Novo, Anael
A1 Dacal, Andrés
A1 Calviño Costas, Consuelo
A1 Lancho, Angel
A1 Amigo Lechuga, Jorge
A1 Bello, Xabier
A1 Cameselle Teijeiro, José Manuel
A1 Carracedo Álvarez, Ángel
A1 Colas, Chrystelle
A1 Muleris, Martine
A1 Wimmer, Katharina
A1 Ruiz Ponte, Clara
K1 Lynch syndrome
K1 CMMRD
K1 Phenotypic continuum
K1 Genetic modifiers
K1 Whole-exome sequencing
AB 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.
PB MDPI
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21176
UL http://hdl.handle.net/10347/21176
LA eng
NO Fernández-Rozadilla, C.; Alvarez-Barona, M.; Schamschula, E.; Bodo, S.; Lopez-Novo, A.; Dacal, A.; Calviño-Costas, C.; Lancho, A.; Amigo, J.; Bello, X.; Cameselle-Teijeiro, J.M.; Carracedo, A.; Colas, C.; Muleris, M.; Wimmer, K.; Ruiz-Ponte, C. Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum. Cancers 2019, 11, 1081
NO This research was funded by Spanish National Centre for Genomic Analysis (CNAG, Barcelona). This work was supported by the 2013 CNAG call: 300-exomes to elucidate Rare-Diseases to C.R.-P
DS Minerva
RD 23 abr 2026