Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration

Abstract

The discovery of circulating tumour DNA molecules created a paradigm shift in tumour biomarkers as predictors of recurrence. Non-invasive prenatal testing (NIPT) to detect circulating cell-free foetal DNA in maternal plasma is increasingly recognised as a valuable substitute to perceive foetal copy number variation (CNV). This study aimed to determine whether the copy number detection in plasma samples using NIPT platform could be used as a prognostic biomarker in patients with gynaecological cancer. We conducted a prospective study using samples containing preoperative plasma from 100 women with gynaecological cancers. Samples were randomly rearranged and blindly sequenced using a low-coverage whole-genome sequencing plasma DNA, NIPT platform. The NIPT pipeline identified copy number alterations (CNAs) were counted in plasma as a gain or loss if they exceeded 10 Mb from the expected diploid coverage. Progression-free survival (PFS) and overall survival (OS) were analysed according to the presence of CNA in plasma using Kaplan–Meier analyses. The NIPT pipeline detected 19/100 cases of all gynaecological cancers, including 6/36 ovarian cancers, 3/11 cervical cancers, and 10/53 endometrial cancers. Patients with CNA in plasma had a significantly poorer prognosis in all stages concerning PFS and OS. Therefore, low-coverage sequencing NIPT platform could serve as a predictive marker of patient outcome.

Liquid biopsy in endometrial cancer

“…The same findings were obtained for the evaluation of CNV in ECs by NGS by Nakabayashi et al [54] on three patients on the following loci: 1p36-p31 and 1q12-q44 or 8q24.…”

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT

“…These findings suggest that the screening and evaluation of cfDNA by blood sampling could be a potential predictor of cancer. Detection of the copy number in plasma samples using an NIPT platform has reportedly been used as a prognostic biomarker in patients with gynecological cancer . Our data suggest that invasive prenatal procedures should be recommended without retesting in women with altered genomic profiles, since the likelihood of obtaining reliable results is relatively low for plasma samples exhibiting multiple copy number variations that can influence fetal mortality.…”

Low-Coverage Sequencing of Urine Sediment DNA for Detection of Copy Number Aberrations in Bladder Cancer

“… 11–14 , 18 Following recent developments in sequencing technology, next-generation sequencing has become widely used in noninvasive prenatal testing chromosome copy number detection due to its high throughput, high sensitivity, and low cost. 19–25 Therefore, we presumed that low-coverage sequencing could be used to detect chromosomal copy number variation, in combination with bladder cancer urine sediment samples to detect copy number variation in exfoliated cells from urine sediment for the diagnosis and monitoring of bladder cancer.…”