Gestational trophoblastic neoplasia (GTN) represents a group of diseases characterized by production of
human chorionic gonadotropin (hCG). Since non-gestational
tumors may occasionally secrete hCG, histopathological diagnosis is important for appropriate clinical management. However, a histopathological diagnosis is not always available. We therefore investigated the feasibility of extracting
cell free DNA (
cfDNA) from the plasma of women with GTN for use as a "liquid biopsy" in patients without histopathological diagnosis.
cfDNA was prepared from the plasma of 20 women with a diagnosis of GTN and five with hCG-secreting
tumors of unknown origin. Genotyping of
cfDNA from the patient, genomic
DNA from her and her partner and
DNA from the
tumor tissue identified
circulating tumor DNA (ctDNA) (from 9% to 53% of total
cfDNA) in 12 of 20 patients with GTN. In one case without a tissue diagnosis, ctDNA enabled a diagnosis of GTN originating in a non-molar conception and in another a diagnosis of non-gestational
tumor, based on the high degree of allelic instability and loss of heterozygosity in the ctDNA. In summary ctDNA can be detected in the plasma of women with GTN and can facilitate the diagnosis of both gestational and non-gestational
trophoblastic tumors in cases without histopathological diagnosis.