Variants of Fumarate Hydratase Gene in Uterine Disorders: A Clinical Trial

Abstract

The dysregulation of metabolism is a hallmark of cancer. Enzymes of tricarboxylic acid (TCA) cycle have a key role in pathogenesis of carcinogenesis as oncometabolits. The variants in fumarate hydratase (FH) gene have been linked to sporadic tumors and familial tumor propensity. To asses the prevalence of variants in the FH gene in endometrial carcinoma (EC) and uterine leiomyomas (UL). Material and Methods: This prospective study included 58 patients with EC and 44 with UL. The FH gene variants were analyzed in the DNA samples collected from peripheral circulation. All exons of the FH gene were replicated by polymerase chain reaction utilizing specific primers including intron-exon boundaries and than was sequenced with Sanger method. Results: Only two variants were detected in two different patients. The c.927G>A (p.Pro309Pro) and c.63C>T (p.Ala21Ala) variants were observed in patients with UL, EC respectively. c.927G>A (p.Pro309=) and c.63C>T (p.Ala21=) are rare variants inside the overall population with allele frequency ranges of 0.02428, 0.000014 respectively. Conclusion: The contribution of variants in genes encoding the TCA cycle enzymes in tumor cells has provided understanding fundamental role on metabolic alterations in carcinogenesis. Further studies are needed to discover the novel tumor mutations and identify appropriate treatment.