مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Novel Genetic Clues Linking Endometriosis and Endometrial Stromal Sarcoma: Insights from Whole Exome Sequencing
Novel Genetic Clues Linking Endometriosis and Endometrial Stromal Sarcoma: Insights from Whole Exome Sequencing
Zahra Allahyar,1,*Mona khosravifar,2Kiandokht Kiani,3Amir Amiri-yekta,4
1. 1. Department of Genetics, Faculty of Sciences and Advanced Biological Technologies, University of Science and Culture, Tehran, Iran 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 3. 3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 4. 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Introduction: Endometriosis and endometrial stromal sarcoma (ESS) are hormonally modulated gynecologic disorders with distinct biological behavior. While endometriosis is a benign, estrogen-dependent inflammatory condition, ESS is a rare uterine malignancy with poorly characterized molecular features. Investigating patients who present with both conditions may uncover shared pathogenic pathways and novel cancer susceptibility genes
Methods: We performed whole exome sequencing (WES) on a 53-year-old woman diagnosed with histologically confirmed endometriosis and ESS. The patient had two live births and a family history notable for uterine fibroids, endometriosis, and infertility. Sequencing data were filtered for rare variants based on minor allele frequency (<1%), predicted pathogenicity, and biological relevance to cancer, apoptosis, or reproductive system function.
Results: WES revealed potentially pathogenic variants in CACNA1E, DZIP1L, TMC1, ZC3H15, NAA35, UNC5C, SLC33A1, SMPD1, and VSNL1. Among these, UNC5C, a netrin receptor involved in apoptosis, has been implicated as a tumor suppressor in endometrial and ovarian cancers. SMPD1 and VSNL1 have shown altered expression profiles in multiple malignancies, though their roles in female reproductive disease remain undefined. The remaining genes have not been previously linked to gynecologic pathology and may represent novel candidate genes or genetic modifiers.
Conclusion: This case demonstrates the utility of WES in identifying rare and potentially novel variants in patients with overlapping gynecologic conditions. Variants in UNC5C and associated apoptotic or signaling pathways may play a role in both endometriosis progression and malignant transformation. Further functional studies and multi-case comparisons are warranted to validate these findings and elucidate their mechanistic contributions. In addition, targeted PCR amplification followed by Sanger sequencing is necessary to confirm the identified variants before proceeding to downstream functional characterization.