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