Abstract
BackgroundGestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. Despite the frequently aggressive clinical nature, choriocarcinoma has been routinely curable with cytotoxic chemotherapy for over 50 years. To date little is known regarding the route to oncogenesis in this malignancy.MethodsIn a case of intraplacental choriocarcinoma, we have performed detailed genetic studies including microsatellite analysis, whole genome sequencing (WGS) and methylation analysis of the tumour and surrounding mature placenta.ResultsThe results of the WGS sequencing indicated a very low level of mutation and the absence of any driver mutations or oncogene activity in the tumour. The methylation analysis identified a distinctly different profile in the tumour from that of the mature placenta. Comparison with a panel of reference methylation profiles from different stages of placental development indicated that the tumour segregated with the first trimester samples.ConclusionsThese findings suggest that gestational choriocarcinoma is likely to arise as a result of aberrations of methylation during development, rather than from DNA mutations.The results support the hypothesis that gestational choriocarcinoma arises from a normally transient early trophoblast cell. At this point in development this cell naturally has a phenotype of rapid division, tissue invasion and sensitivity to DNA damaging chemotherapy that is very similar to that of the mature choriocarcinoma cell.
Highlights
Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta
Fluorescent microsatellite genotyping analysis The fluorescent microsatellite genotyping analysis (Additional file 2: Table S2) demonstrated the tumour to have the same genotype as the healthy placenta, confirming the identity of the tumour as a non-molar gestational choriocarcinoma arising in the current pregnancy
Methylation studies In contrast the epigenetic studies demonstrated that the pattern of methylation is markedly different between the tumour, the surrounding normal placenta or reference unrelated term placental samples
Summary
Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. The overall incidence of gestational choriocarcinoma is estimated at 1 case per 50,000 pregnancies and aside from increasing maternal age does not appear to have any other significant risk factors [2] Despite this rarity and the rapidity of cell growth, gestational choriocarcinoma has been curable with cytotoxic chemotherapy since the 1950s and in modern series the overall cure rate approaches 95% [3, 4]. It has been suggested that gestational choriocarcinoma may not necessarily represent a classical mutation based malignant transformation Instead these tumours could arise due to the persistence of early trophoblast cells, which have failed to either mature or undergo apoptosis [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
