RT Journal Article
SR Electronic
T1 Prevalence of <em>MLH1</em> constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 498
OP 502
DO 10.1136/jmedgenet-2015-103076
VO 52
IS 7
A1 Castillejo, Adela
A1 Hernández-Illán, Eva
A1 Rodriguez-Soler, María
A1 Pérez-Carbonell, Lucía
A1 Egoavil, Cecilia
A1 Barberá, Victor M
A1 Castillejo, María-Isabel
A1 Guarinos, Carla
A1 Martínez-de-Dueñas, Eduardo
A1 Juan, María-Jose
A1 Sánchez-Heras, Ana-Beatriz
A1 García-Casado, Zaida
A1 Ruiz-Ponte, Clara
A1 Brea-Fernández, Alejandro
A1 Juárez, Miriam
A1 Bujanda, Luis
A1 Clofent, Juan
A1 Llor, Xavier
A1 Andreu, Montserrat
A1 Castells, Antoni
A1 Carracedo, Angel
A1 Alenda, Cristina
A1 Payá, Artemio
A1 Jover, Rodrigo
A1 Soto, José-Luis
YR 2015
UL http://jmg.bmj.com/content/52/7/498.abstract
AB 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&lt;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.