Purpose: To investigate the genes of patients with sporadic endometrial cancer (EC) and suspected Lynch syndrome (LS)-related EC in the Chinese population. Identification of meaningful mutation sites can provide theoretical basis for molecular targeted therapy, aiming to improve the prognosis of patients with EC.
Methods: We recruited 388 patients with EC for mismatch repair (MMR) immunohistochemistry and MLH1 methylation analysis. Based on the results, they were divided into four groups: MMR without deletion group (sporadic EC group 1); MLH1&PMS2 deletion and MLH1 methylation group (sporadic EC group 2); MSH2 and/or MSH6 deletion group (suspected LS group); and unclassified group (remainder cases). Patients from each group were randomly screened for whole-exome sequencing detection. Genome Analysis Toolkit, VarScant, MuTect, and CONTRA were used to detect the insertions/deletions, single nucleotide polymorphisms, and copy number variations. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery. Protein–protein interaction analysis was accomplished through the STRING database.
Results: The MMR immunohistochemistry results were positive (without MMR deletion) and negative in 299 patients and 89 patients, respectively. The 32, 10, 13, and 7 patients in the sporadic EC group 1, sporadic EC group 2, suspected LS group, and unclassified group were randomly selected for whole-exome sequencing, respectively. These three groups had a total of 86 common mutation sites, which were distributed on 26 genes. Among the top 30 common high-frequency mutation sites, 12, 5, 4, and 3 mutation sites were located on HNRNPCL1 , PRAMEF1 , HNRNPCL2 , and CFAP74 , respectively. Protein–protein interaction analysis showed that DFFB  was associated with the most genes. There were some differences in the number of specific mutations in the families of different LS-related EC proband.
Conclusion: HNRNPCL1, PRAMEF1, CFAP74, and DFFB  may be potential biomarkers for EC or LS-related EC.
Keywords: endometrial cancer, Lynch syndrome, whole-exome sequencing, WES, mismatch repair gene, gene mutation