Work

Whole genome doubling in adenomyosis

Year: 2024

Type: article

Abstract: Dear Editor, Whole genome doubling (WGD) was found to be associated with an early onset of the disease and a higher response rate to endocrine therapy among adenomyosis (AM) patients.The clinical manifestation could not be explained by commonly found driver genes in AM and endometriosis (EM).AM is one of the most common benign gynecologic diseases.The prevalence of AM has been estimated to range from 5% to 70%, 1-3 with the highest incidence observed in women in their 40s.4,5 Despite various conservative treatment regimens for preserving fertility in women with AM. 6,7 Currently there are no reliable strategies for predicting its occurrence and exacerbation.WGD events are defined if the ploidy of the major allele exceeds 1.5 on at least 50% of at least 11 autosomes.8 While WGD events have been extensively explored in tumorigenesis, metastasis, treatment, and prognosis of solid tumours, little is known about WGD in the context of AM.Thus, the aims of this study are to analyze the genomic and transcriptomic characteristics of eutopic and ectopic endometrium harvested from patients with AM and EM.This study included a total of 79 AM patients, 22 EM patients and 20 controls (Tables S1-S3).Fresh samples of endometrium, AM lesions, and EM lesions were obtained using aseptic procedures.Paired peripheral blood samples were collected preoperatively within one day before surgery and anaesthesia.Tissue samples were sent for whole exome sequencing (WES) analysis, RNAsequencing, and pathological evaluation to ensure accurate histological diagnosis.The analysis of allele-specific DNA copy number was used to determine the WGD status.B-allele frequency values (BAF) and log R values were calculated based on read coverage and GC content in the same region of different specimen types.Ploidy levels were interpreted from BAF and log R values using the ASCAT software.9 WGD was detected in 33 samples from 29 patients (Figure 1A,B).The median ploidy was 3.9 (range: 3.3-4.6) in WGD samples, compared to 2.0 (range: 1.9-2.4) in non-WGD samples (Wilcoxon rank sum test,

Source: Clinical and Translational Medicine

DOI: 10.1002/ctm2.1809