title: Circulating Cell Free DNA in the Diagnosis of Trophoblastic Tumors.
abstract: 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.
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Openshaw
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Harvey
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Baljeet
authors.initials: B
authors.lastname: Kaur
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sarwar
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.affiliation: Trophoblastic Tumour Screening & Treatment Centre, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Fisher
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D004247:DNA / Q000097:blood*; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA
keywords: Cell free DNA; Circulating tumor DNA; Hydatidiform mole; Liquid biopsy; Molecular genotyping; Trophoblastic tumor