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

Sci Rep. 2018 Jul 25;8(1):11205. doi: 10.1038/s41598-018-29381-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell-Free Nucleic Acids / blood*
  • Cell-Free Nucleic Acids / genetics
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Testing
  • Genital Neoplasms, Female / blood*
  • Genital Neoplasms, Female / classification
  • Genital Neoplasms, Female / genetics
  • Genital Neoplasms, Female / pathology
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Middle Aged
  • Progression-Free Survival
  • Sequence Analysis, DNA
  • Whole Genome Sequencing

Substances

  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA