A case of intraplacental gestational choriocarcinoma; Characterised by the methylation pattern of the early placenta and an absence of driver mutations

Savage, Philip, Monk, David, Hernandez Mora, Jose R., Van Der Westhuizen, Nick, Rauw, Jennifer, Tinker, Anna, Robinson, Wendy, Song, Qianqian, Seckl, Michael J. and Fisher, Rosemary A. (2019) A case of intraplacental gestational choriocarcinoma; Characterised by the methylation pattern of the early placenta and an absence of driver mutations. BMC Cancer, 19 (1). ISSN 1471-2407

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Background: Gestational 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. Methods: In 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. Results: The 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. Conclusions: These 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.

Item Type: Article
Additional Information: Funding Information: There was no specific funding for this project. JHM and DM are been funded in part by Ministerio de Economía, Industria y Competitividad (MINECO), which is part of Agencia Estatal de Investigación (AEI), through the projects BFU2014–53093-R and BFU2017–85571-R (Co-funded by European Regional Development Fund; ERDF, a way to build Europe). We thank CERCA Programme / Generalitat de Catalunya for institutional support. RAF acknowledges the support of the UK Department of Health and the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre for funding for the DNA preparation and microsatellite genotyping. MJS acknowledges support from the Imperial National Institute of Health Research (NIHR) Biomedical Research Centre and NIHR/ Cancer Research UK Experimental Cancer Medicine Centre. Publisher Copyright: © 2019 The Author(s).
Uncontrolled Keywords: chemotherapy,choriocarcinoma,epigenetics,methylation,oncogenesis,placenta,pregnancy,trophoblast,oncology,genetics,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2022 12:30
Last Modified: 07 Nov 2022 00:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/89561
DOI: 10.1186/s12885-019-5906-8

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