Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer

Adela Castillejo, Eva Hernández-Illán, María Rodriguez-Soler, Lucía Pérez-Carbonell, Cecilia Egoavil, Victor M. Barberá, María Isabel Castillejo, Carla Guarinos, Eduardo Martínez-de-Dueñas, María Jose Juan, Ana Beatriz Sánchez-Heras, Zaida García-Casado, Clara Ruiz-Ponte, Alejandro Brea-Fernández, Miriam Juárez, Luis Bujanda, Juan Clofent, Xavier Llor, Montserrat Andreu, Antoni CastellsAngel Carracedo, Cristina Alenda, Artemio Payá, Rodrigo Jover, José Luis Soto

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18 Scopus citations

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 ligationdependent 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<0.0001). No constitutional epimutations in MLH1 were detected in the unselected population (0/62); five cases from the selected series were positive for MLH1 epimutations (15.6%, 5/32; p=0.004). Conclusions Our results suggest a negligible prevalence of MLH1 constitutional epimutations in unselected cases of CRC. Therefore, MLH1 constitutional epimutation analysis should be conducted only for patients who fulfil the rBG and who lack MLH1 expression with methylated MLH1.
Original languageAmerican English
Pages (from-to)498-502
Number of pages5
JournalJournal of Medical Genetics
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

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    Castillejo, A., Hernández-Illán, E., Rodriguez-Soler, M., Pérez-Carbonell, L., Egoavil, C., Barberá, V. M., Castillejo, M. I., Guarinos, C., Martínez-de-Dueñas, E., Juan, M. J., Sánchez-Heras, A. B., García-Casado, Z., Ruiz-Ponte, C., Brea-Fernández, A., Juárez, M., Bujanda, L., Clofent, J., Llor, X., Andreu, M., ... Soto, J. L. (2015). Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer. Journal of Medical Genetics, 498-502. https://doi.org/10.1136/jmedgenet-2015-103076