A Sensitive and Transparent Method for Tumor-Informed Detection of Circulating Tumor DNA in Ovarian Cancer Using Whole-Genome Sequencing

Christine Fribert Thusgaard & Kirsten Marie Jochumsen et al. · 2024-12-12

Circulating tumor DNA (ctDNA) is a biomarker that could potentially improve the survival rate of ovarian cancer (OC), e.g., by monitoring treatment response and early relapse detection. However, an optimal method for ctDNA analysis in OC remains to be established. We developed a method for tumor-informed single-nucleotide variant detection of ctDNA in OC using whole-genome sequencing. Tumor and plasma samples obtained at the time of diagnosis from 10 patients with OC were included. The tested method involved applying basic filters with different cut-offs of read depth, allelic depth, and variant allele frequency of tumor and normal DNA. In addition, we applied a new filtering approach using plasma samples from the other included OC patients (the plasma pool) for specific removal of artefacts. The basic filters with varying cut-offs showed minor improvement in signal-to-noise ratio (S2N). However, the addition of the plasma pool filter resulted in a considerable ctDNA signal improvement, indicated by both S2N and z-score. This study demonstrates a promising method for ctDNA detection in OC patients using a tumor-informed approach for whole-genome sequencing. Despite the limited number of patients involved, the results suggest a significant potential of the method for ctDNA signal detection in patients with OC.

Links
DOIPubMed
Journal
International Journal of Molecular Sciences
Institutions
Odense University Hospital
Authors
Christine Fribert Thusgaard, Sepideh Sadegh, Kirsten Marie Jochumsen
Funding
Region of Southern Denmark Grant 18/17528Region of Southern Denmark Grant 20/14090Holms Mindelegat Grant 20035KV Fonden Grant 2020-2665Fonden til Lægevidenskabens Fremme Grant 20-L-0198Aase og Ejnar Danielsens Fond Grant 21-10-0058Dagmar Marshalls Fond Grant Improving survival of ovarian cancer by using circulating tumor DNA as a biomarkerTornøes og Høyrups Legat Grant 32120Region of Southern Denmark Grant R66-A3026Region of Southern Denmark Grant R110-A4580Region of Southern Denmark Grant 20035Region of Southern Denmark Grant 2020-2665Region of Southern Denmark Grant 20-L-0198Region of Southern Denmark Grant 21-10-0058Region of Southern Denmark Grant 32120Odense University Hospital Grant 18/17528Odense University Hospital Grant 20/14090Odense University Hospital Grant R66-A3026Odense University Hospital Grant R110-A4580Odense University Hospital Grant 20035Odense University Hospital Grant 2020-2665Odense University Hospital Grant 20-L-0198Odense University Hospital Grant 21-10-0058Odense University Hospital Grant 32120Holms Mindelegat Grant 18/17528Holms Mindelegat Grant 20/14090Holms Mindelegat Grant R66-A3026Holms Mindelegat Grant R110-A4580Holms Mindelegat Grant 2020-2665Holms Mindelegat Grant 20-L-0198Holms Mindelegat Grant 21-10-0058Holms Mindelegat Grant 32120KV Fonden Grant 18/17528KV Fonden Grant 20/14090KV Fonden Grant R66-A3026KV Fonden Grant R110-A4580KV Fonden Grant 20035KV Fonden Grant 20-L-0198KV Fonden Grant 21-10-0058KV Fonden Grant 32120Fonden til Lægevidenskabens Fremme Grant 18/17528Fonden til Lægevidenskabens Fremme Grant 20/14090Fonden til Lægevidenskabens Fremme Grant R66-A3026Fonden til Lægevidenskabens Fremme Grant R110-A4580Fonden til Lægevidenskabens Fremme Grant 20035Fonden til Lægevidenskabens Fremme Grant 2020-2665Fonden til Lægevidenskabens Fremme Grant 21-10-0058Fonden til Lægevidenskabens Fremme Grant 32120Aase & Ejnar Danielsens Fond Grant 18/17528Aase & Ejnar Danielsens Fond Grant 20/14090Aase & Ejnar Danielsens Fond Grant R66-A3026Aase & Ejnar Danielsens Fond Grant R110-A4580Aase & Ejnar Danielsens Fond Grant 20035Aase & Ejnar Danielsens Fond Grant 2020-2665Aase & Ejnar Danielsens Fond Grant 20-L-0198Aase & Ejnar Danielsens Fond Grant 21-10-0058Aase & Ejnar Danielsens Fond Grant 32120Tornøes & Høyrups Legat Grant 18/17528Tornøes & Høyrups Legat Grant 20/14090Tornøes & Høyrups Legat Grant R66-A3026Tornøes & Høyrups Legat Grant R110-A4580Tornøes & Høyrups Legat Grant 20035Tornøes & Høyrups Legat Grant 2020-2665Tornøes & Høyrups Legat Grant 20-L-0198Tornøes & Høyrups Legat Grant 21-10-0058Tornøes & Høyrups Legat Grant 32120Dagmar Marshalls Fond Grant 18/17528Dagmar Marshalls Fond Grant 20/14090Dagmar Marshalls Fond Grant R66-A3026Dagmar Marshalls Fond Grant R110-A4580Dagmar Marshalls Fond Grant 20035Dagmar Marshalls Fond Grant 2020-2665Dagmar Marshalls Fond Grant 20-L-0198Dagmar Marshalls Fond Grant 21-10-0058Dagmar Marshalls Fond Grant 32120