Mutation detection in women diagnosed with endometrial cancer: a next-generation sequencing analysis.

Abstract

Endometrial cancer (EC) is a heterogeneous gynecological malignancy characterized by diverse genetic and epigenetic alterations. This study investigated genetic mutations associated with EC among Kurdish women using next-generation sequencing (NGS). Seventy histopathologically confirmed EC cases were included, and peripheral blood DNA samples were analyzed. Whole-exome sequencing was performed on nine carefully selected cases based on specific clinical and pathological criteria, including early age of onset and/or family history suggestive of hereditary cancer predisposition, following enzymatic fragmentation, adapter ligation, PCR amplification, and targeted capture using biotinylated probes. The analysis identified five potentially significant variants in five genes: CHEK2, MUTYH, PLA2G2A, POLE, and USF3. The detected alterations included a heterozygous deletion in CHEK2 (p. Tyr113del), a homozygous SNP in MUTYH (p. Arg217His), heterozygous SNPs in PLA2G2A (p. Arg77Gly) and POLE (p. Ser2237Arg), and a heterozygous deletion in USF3 (p. Val576del). These findings highlight important molecular features of EC in Kurdish patients and may support future development of targeted therapeutic strategies. Further validation with larger cohorts is recommended.