Results from a new study of three prototype genome sequencing assays suggest that early detection of different cancers may be possible with high specificity.
Early detection of cancer can mean the difference between the successful and unsuccessful treatment of this deadly disease. The company GRAIL, Inc. was founded to develop blood tests for the early detection of cancer using high-intensity sequencing, population-scale clinical studies, and state-of-the-art computer science and data science.
Initial results of GRAIL’s Circulating Cell-Free Genome Atlas (CCGA) Study, reported recently by the company, are promising.
The CCGA study is designed to characterize the landscape of cell-free nucleic acid (cfNA) profiles in people with and without cancer. The company plans to enroll more than 15,000 patients in the US and Canada, approximately 70% of which will be newly diagnosed cancer patients that have not yet received treatment.
The first CCGA sub-study investigated three prototype sequencing assays as potential methods for a blood-based test for early cancer detection. Blood samples from 878 participants with newly diagnosed cancer who had not yet received treatment and 580 participants without diagnosed cancer, were sequenced with all three prototype assays. Twenty different cancer types across all stages were included in the sub-study.
The three assays included:
- Targeted sequencing of paired cfDNA and white blood cells to detect somatic mutations such as single nucleotide variants and small insertions and/or deletions;
- Whole-genome sequencing of paired cfDNA and white blood cells to detect somatic copy number changes; and
- Whole-genome bisulfite sequencing of cfDNA to detect abnormal cfDNA methylation patterns.
The results of this initial sub-study suggest that using blood tests for early cancer detection may be possible with greater than 99% selectivity. High specificity is essential to avoid false-positive results. In the study, for those patients without a cancer diagnosis, a “cancer-like” signal was found in less than one percent (5 out of 580). Two of the five people were subsequently diagnosed with cancer, and follow up of the other three is ongoing.
Notably, the three prototype assays detected a strong biological signal in cancer types that are typically not screened for and have low survival rates, including lung, ovarian, pancreatic, liver, and esophageal cancers. The signal was detected across all stages of cancer, and increased with the stage. The assays evaluating the entire genome provided the best results, with the whole-genome bisulfite assay giving the strongest performance.