Mutational Analysis of EZH2 Gene in Patients with Colorectal Adenoma Reveals a Genetic Variant Associated with Risk of Malignant Transformation.

Background: Several studies have revealed that chromatin modifications lead to activation or repression of multiple genes including oncogenes and tumor suppressor genes. Inactivation mutation in EZH2 gene would result in activation of oncogenes. The aim of this case-control study was to identify mutations in the EZH2 gene, to study their prevalence among Jordanian patients with colorectal adenoma and to determine how these mutations could be related to colorectal cancer (CRC) progression.

Methods: EZH2 gene sequencing was done by Sanger method for 100 DNA samples, extracted from blood of 50 patients, and 50 controls. Sequencing results were analyzed by Chromaspro and mutational effects were predicted by Mutation Taster bioinformatics tool.

Results: Four variants were identified in Jordanian patients with adenoma; Two novel variantsc.1941T>A and c.2201G>C and two reported variants, g.73038C>T and g.75508A>C. g.73038C>T is the most common germline variant identified in this study. A significant association between the presence of c.2201G>C mutation and colorectal adenoma was found (p value < 0.05).

Conclusion: The present study identified several variants in EZH2 gene among Jordanians with colorectal adenoma.