77P - Whole-exome mutation profiling of cfDNA from over 2000 samples in major cancer indications

Background

Cell-free DNA (cfDNA) has been widely used for patient screening, treatment response and disease progression monitoring. Due to the low tumor fraction of cfDNA samples, assays with small target panel (covering a few hundred genes or less) and high sequencing depth were commonly used. There is a lack of large panels, especially genome-wide whole exome sequencing data based on cfDNA. Here we present cfDNA whole exome sequencing mutational profiles from over 2000 plasma and urine samples in various cancer indications.

Methods

The PredicineWES+ assay, featuring enhanced 20,000x coverage in 600 cancer-related genes (0.25% LoD) and 2,500x in the rest of the exome (1% LoD), was utilized for cfDNA mutation profiling. Requiring as little as 5 ng of cfDNA from 1-5 mL of plasma or 20-40 mL of urine, the assay was performed at various clinical points. Using the Predicine DeepSEA bioinformatics pipeline, it detects SNVs, small insertions and deletions, gene-level CNVs, and targeted rearrangements/fusions, and also reports on MSI, TMB, and tumor fraction. Optionally, it includes low-pass whole-genome sequencing to provide additional genome-wide CNB and tumor fraction data without requiring extra sample volume.

Results

We present data from a representative cohort of over 2,000 blood and urine samples processed at Predicine lab in Hayward, California. These samples span seven major cancer types: breast, lung, prostate, bladder, pancreatic, colon, and head and neck. We compare the mutational and CNV profiles from each liquid biopsy cancer cohort to variants found in solid tumor tissues, using Predicine's in-house data and large public datasets, including Project GENIE (71,817 patients) and other study programs such as TCGA and cBioPortal (38,619 patients).

Conclusions

PredicineWES+ is a comprehensive assay for detecting cancer variants in blood and urine. It detects mutations across 600 cancer-related genes at a 20,000x sequencing depth, with cfDNA mutation profiles that align closely with public tissue datasets. PredicineWES+ is utilized for baseline profiling in the PredicineBEACON MRD assay and demonstrates a high correlation in TMB scores with PredicineATLAS. Available in the US and China, it supports clinical patient testing and global trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Du: Financial Interests, Personal, Full or part-time Employment: Predicine. All other authors have declared no conflicts of interest.