Low-Coverage Whole Genome Sequencing Diagnoses Endometrial Carcinoma from Tampon DNA of Uterine Bleeding Patients
Abstract Background Endometrial carcinoma (EC) is a disease predominantly affecting postmenopausal women. It accounts for about 5% of abnormal uterine bleeding. It is still challenging to diagnose cancers from uterine bleeding patients. Previously, chromosome aberrations were found to be frequent in EC. Here we employed a low coverage whole genome sequencing technology to investigate chromosome aberrations in tampon-collected DNA of patients with suspicious EC. Methods Thirty ECs and 14 benign cases with abnormal bleeding are prospectively recruited. Tampons were used to collect exfoliated cells and DNA extracted from these exfoliated cells was analyzed by a customized bioinformatics workflow, uterine exfoliated cell chromosomal aneuploidy detector (UterCAD). Results As our data shown, frequent chromosome copy number variations (CNV) were found in EC patients as compared to non-tumor controls, especially the chromosome 8q gain and 10q gain. Using UterCAD, CNVs were detected in tampon-derived DNA from 83.3% (25/30) EC, which were 80.8% (21/26) EECs and 100% (4/4) USCs. In EEC group, CNVs were found in 81.3% (13/16), 85.7% (6/7), and 66.7% (2/3) patients of stage IA, IB, and II/III, respectively. Moreover, all the 4 USC patients presented significant CNVs. Conclusions UterCAD could be a highly specific, robust uterine cancer diagnosis method, with an especially high sensitivity for the more aggressive subtype - serous carcinoma. It may be used as a non-invasive approach for diagnosis and active surveillance in endometrial cancer prior to the use of biopsy, thereby largely reducing the treatment burden on patients.