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Circulating Plasma DNA Potentially Identifies Incipient Tumors

By LabMedica International staff writers
Posted on 06 Mar 2019
Early cancer diagnosis might improve survival rates. More...
As circulating tumor DNA (ctDNA) carries cancer-specific modifications, it has great potential as a noninvasive biomarker for detection of incipient tumors.

A recent study describes another potential breakthrough by analyzing cell-free DNA (cfDNA) to identify imbalances in genome-wide copy number alterations (CNA) as a means of screening healthy individuals for cancers. Identifying tumors at early stages would offer the possibility of improved survival rates.

A team of Belgian and Dutch investigators led by those at the University Hospitals Leuven (Leuven, Belgium) developed a unique genomic profiling method for cfDNA called The Genomic Imbalance Profiling from cfDNA SEQuencing (GIPseq) method. The team collected cfDNA samples from 1,002 elderly Belgian patients with no prior history of cancer, and they used GIPseq to look for chromosomal aberrations that suggested the presence of a malignancy. Six-month clinical analyses took place in cases where aberrations were found, with investigators cataloguing any CNAs present in cfDNA to create a “map” of aberrations found in this aging population.

The scientists reported that in 3% of participants chromosomal imbalances were detected. Follow-up analyses, including whole-body MRI screening, confirmed the presence of five hematologic malignancies: one Hodgkin lymphoma (HL), stage II; three non-HL (type chronic lymphocytic leukemia, Rai I–Binet A; type small lymphocytic lymphoma (SLL), stage III; type mucosa-associated lymphoid tissue, stage I) and one myelodysplastic syndrome with excess blasts, stage II. The CNAs detected in cfDNA were tumor-specific. Furthermore, one case was identified with monoclonal B-cell lymphocytosis, a potential precursor of B-cell malignancy. In 24 additional individuals, CNAs were identified but no cancer diagnosis was made. For nine of them, the aberrant cfDNA profile originated from peripheral blood cells. For 15 others the origin of aberrations in cfDNA remains undetermined.

The authors concluded that their results illustrated the GIPseq’s effectiveness in detecting incipient hematologic malignancies and clonal mosaicism with unknown clinical significance in healthy patients. They demonstrated that cfDNA screening detects CNAs, which are not only derived from peripheral blood, but even more from other tissues. Since the clinical relevance of clonal mosaics in other tissues remains unknown, long-term follow-up is warranted. The study was published January 1, 2019, in the journal Annals of Oncology.

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University Hospitals Leuven


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