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Combining copy number, methylation markers, and mutations as a panel for endometrial cancer detection via intravaginal tampon collection

Gynecologic Oncology Dec 11, 2019

Sangtani A, Wang C, Weaver A, et al. - Researchers evaluated if endometrial cancer (EC) could be identified in shed DNA obtained with vaginal tampon by examining copy number, methylation markers, and mutations. From 38 EC patients and 28 women with benign indications, they obtained tampons before hysterectomy. On extracted tampon DNA, they performed low-coverage whole genome sequencing to evaluate copy number, pyrosequencing to determine percent promotor methylation of HOXA9, RASSF1, and CDH13 and next generation sequencing to recognize mutations in 19 genes related to EC detected through The Cancer Genome Atlas. The highest specificities but lowest sensitivities (37–40% sensitivity; 100% specificity for HOXA9, RASSF1 and HTR1B) were afforded by methylation analysis, while improved sensitivity (50% sensitivity; 83% specificity) of mutation analysis was evident. In women with benign surgical indications, they recognized only one “false positive” result for copy number variants, which relied on disclosure of copy number alterations and related to a leiomyosarcoma that was only identified at hysterectomy. Taking into account any of the 3 biomarker classes as a positive, led to a sensitivity and specificity of 92% and 86%, respectively. A proof-of-principle for non-invasive yet accurate identification of endometrial cancer was shown. Experts suggested that a clinically useful test for identifying EC may likely be developed with improved biomarker testing.
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