4159 - Unbiased genomewide screening of circulating plasma DNA for cancer detection

Background

Early cancer diagnosis might significantly improve survival rates. As circulating tumor (ctDNA) carries cancer-specific modifications, it has great potential as a non-invasive biomarker for detection of incipient tumors.

Methods

Cell-free DNA (cfDNA) samples of 1006 elderly people (389 men and 617 women), not having any history of malignancy, were collected between October 2015 and September 2017 and analyzed via our cfDNA analysis pipeline, coined GIPseq (Genomic Imbalance Profiling from cfDNA SEQuencing). GIPseq profiles were screened for the presence of (sub)chromosomal copy number variations (CNVs) that might be predictive for a malignancy. When imbalances were detected, a 6-month clinical follow-up was performed.

Results

In 3% of participants (20 men and 10 women) an aberrant GIPseq profile was detected. Detected gains and losses in cfDNA were reproducible upon analysis of a second plasma sample taken within a mean time span of 139 days. Subsequent whole body MRI screening led to the identification of 3 hematological malignancies (1 Hodgkin stage II; 1 non-Hodgkin stage IV; 1 myelodysplastic syndrome with excess blasts stage II) and 2 cases with monoclonal B-cell lymphocytosis, a potential precursor of B-cell malignancy. The CNVs detected in plasma cfDNA were confirmed to be tumor-specific upon shallow sequencing of biopsy DNA. In 24 individuals, chromosomal anomalies in cfDNA could not be linked to a malignancy. Eleven of these cases had a CNV on chromosome 5 (5q-, n = 2 cases), 15 (15+, n = 5) or 20 (20q-, n = 4) in cfDNA, which was found to originate from peripheral blood cells in 7 of them. Previous studies found that mosaicisms for large chromosomal anomalies are detectable in cellular DNA of peripheral blood and buccal cells in about 2% of elderly people, predicting a 5 to 10-fold enhanced risk of a subsequent cancer. For 16 of our study participants, the cellular origin of the chromosomal anomalies detected in cfDNA remains unknown.

Conclusions

Our results deliver unique data on the presence of a wide range of (cancer-related) chromosomal aberrations detectable in cfDNA of elderly people. A long-term follow-up of these people is planned to further explore the biological and clinical significance of the detected anomalies.

Clinical trial identification

Legal entity responsible for the study

University Hospitals Leuven.

Funding

Research Foundation - Flanders.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.