Circulating Cell Free DNA in the Diagnosis of Trophoblastic Tumors

• Circulating tumor DNA can be detected in the plasma of patients with gestational trophoblastic neoplasia.
• Analysis of circulating tumor DNA may provide a diagnosis in patients with hCG-secreting tumors and no tissue biopsy.
• ctDNA may provide a source of tumor DNA for further investigation of gestational trophoblastic neoplasia.Gestational trophoblastic neoplasia describes a group of pregnancy related cancers. These cancers produce the pregnancy hormone human chorionic gonadotropin (hCG) which is useful in diagnosing and monitoring the disease. Some non-pregnancy related cancers may also make hCG causing difficulty with diagnosis in patients without a biopsy for pathological diagnosis.In this study we detected DNA from the cancer in patients' blood. Analysis of this DNA enabled us to distinguish cancers that were pregnancy related from those that were not. In the future we may use this technology to help diagnose pregnancy related cancers in patients where a biopsy is unavailable.

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.