1. Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer
- Author
-
Cristina Alenda, Rodrigo Jover, José Luis Soto, Zaida García-Casado, Víctor Manuel Barberá, Lucía Pérez-Carbonell, Antoni Castells, Cecilia Egoavil, Miriam Juárez, Eva Hernández-Illán, Maria Rodriguez-Soler, Alejandro Brea-Fernández, Xavier Llor, María Isabel Castillejo, Luis Bujanda, Carla Guarinos, Artemio Payá, Angel Carracedo, Montserrat Andreu, María José Juan, Adela Castillejo, Eduardo Martínez-de-Dueñas, Clara Ruiz-Ponte, Ana Beatriz Sánchez-Heras, Juan Clofent, Universidad de Alicante. Departamento de Biotecnología, Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Biotecnología, and Transducción de Señales en Bacterias
- Subjects
Oncology ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Colorectal cancer ,Molecular Sequence Data ,Population ,Biología Celular ,MLH1 ,DNA Mismatch Repair ,Statistics, Nonparametric ,Germline ,Epigenesis, Genetic ,symbols.namesake ,Internal medicine ,Prevalence ,Genetics ,medicine ,Humans ,Genetic Testing ,Promoter Regions, Genetic ,education ,colon, Clinical genetics, Epigenetics [Cancer] ,neoplasms ,Genetics (clinical) ,MLH1 constitutional epimutations ,Adaptor Proteins, Signal Transducing ,Sanger sequencing ,education.field_of_study ,Base Sequence ,business.industry ,Nuclear Proteins ,nutritional and metabolic diseases ,Sequence Analysis, DNA ,DNA Methylation ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Genética ,Lynch syndrome ,digestive system diseases ,Mutation ,symbols ,Unselected population ,Medical genetics ,MutL Protein Homolog 1 ,business ,Microsatellite Repeats - Abstract
Background The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC). Methods Patients with diagnoses of CRC (n=2123) were included in the unselected group. For comparison, a group of 847 selected patients with CRC who fulfilled the revised Bethesda guidelines (rBG) were also included. Somatic and constitutional MLH1 methylation was assayed via methylation-specific multiplex ligation-dependent probe amplification of cases lacking MLH1 expression. Germline alterations in mismatch-repair (MMR) genes were assessed via Sanger sequencing and methylation-specific multiplex ligation-dependent probe amplification. Results Loss of MLH1 expression occurred in 5.5% of the unselected series and 12.5% of the selected series (p
- Published
- 2015