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Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum

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 journe...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721314/
https://www.ncbi.nlm.nih.gov/pubmed/31366136
http://dx.doi.org/10.3390/cancers11081081
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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
author_facet 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
author_sort Fernández-Rozadilla, Ceres
collection PubMed
description 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.
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spelling pubmed-67213142019-09-10 Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum 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 Cancers (Basel) Communication 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. MDPI 2019-07-30 /pmc/articles/PMC6721314/ /pubmed/31366136 http://dx.doi.org/10.3390/cancers11081081 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
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
Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title_full Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title_fullStr Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title_full_unstemmed Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title_short Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
title_sort early colorectal cancers provide new evidence for a lynch syndrome-to-cmmrd phenotypic continuum
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721314/
https://www.ncbi.nlm.nih.gov/pubmed/31366136
http://dx.doi.org/10.3390/cancers11081081
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