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Although described over a century ago, the genetic and non-genetic drivers remain unclear, while recent work highlights roles for genetics, epigenetics, and microRNAs in initiation and progression. This Review synthesizes current molecular research to clarify GTD pathogenesis and its progression, shifting focus from mainly clinical and diagnostic perspectives to mechanisms that explain disease development and behavior.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/gestational-trophoblastic-disease-understanding-the-molecular-mechanisms-of-placental-tumours/364410/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/gestational-trophoblastic-disease-understanding-the-molecular-mechanisms-of-placental-tumours/364410.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is gestational trophoblastic disease (GTD)?","Question",{"text":112,"@type":113},"GTD is a group of rare benign and cancerous lesions arising from trophoblast cells of the placenta. These lesions can form abnormal molar tissue or progress to cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is GTD classified into benign and malignant forms?",{"text":117,"@type":113},"Benign GTD includes hydatidiform mole and atypical placental site nodule (APSN). Malignant forms are collectively termed gestational trophoblastic neoplasia (GTN), including invasive moles, choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumour (ETT).",{"name":119,"@type":110,"acceptedAnswer":120},"Why is studying GTD at the molecular level important?",{"text":121,"@type":113},"Molecular study can improve understanding of pathogenesis and developmental origins, reduce misdiagnosis, and explain high responsiveness and treatment sensitivity. 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Published by The Company of Biologists | Disease Models & Mechanisms (2025) 18, dmm052010 . doi:10 . 1242/dmm.052010  \nREVIEW  \nGestational trophoblastic disease: understanding the molecular mechanisms of placental tumours  \nAlina Nicheperovich1, Benjamin Schuster-Bckler1,* and Mire N Leathlobhair2,*  \nABSTRACT  \n\n| Gestational trophoblastic disease (GTD) describes a group of rare benign and cancerous lesions originating from the trophoblast cells of the placenta. These neoplasms are unconventional entities, being one of the few instances in which cancer develops from the cells of another organism, the foetus. Although this condition was first described over 100 years ago, the specific genetic and non-genetic drivers of this disease remain unknown to this day. However, recent findings have provided valuable insights into the potential mechanisms underlying this rare condition. Unlike previous reviews focused primarily on the clinical and diagnostic aspects of disease development, this Review consolidates the latest research concerning the role of genetics, epigenetics and microRNAs in the initiation and progression of GTD. By examining GTD from a molecular perspective, this Review provides a unique framework for understanding the pathogenesis and progression of this rare disease.\u003Cbr>KEY WORDS: Gestational trophoblastic disease, Gestational trophoblastic neoplasia, Molar pregnancy, Choriocarcinoma, Placental tumour |\n| --- |\n| Introduction\u003Cbr>The human placenta, sharing the same genetic composition asthe foetus, develops from the trophectoderm of the early embryo. This layer gives rise to trophoblast cells, the epithelial-like cells that form the placenta and are crucial for supporting foetal growth and development throughout pregnancy (Box 1) . Gestational trophoblastic disease (GTD) arises from the uncontrolled proliferation of these trophoblast cells, which can lead to the formation of molar tissue, an abnormal mass of cells that fills the uterus, or cancer. GTD is thus broadly classified into two groups: benign and malignant (Fig. 1) . These groups are then further subdivided; benign forms include the hydatidiform mole and the more recently discovered atypical placental site nodule (APSN), a benign lesion that develops from residual placental tissue in the uterus following a delivery or termination of pregnancy. Hydatidiform moles can be classified as complete (CHM) or partial (PHM), primarily based on pathological features (Fig. 1), although genotyping can be used (Fig. 2) . Meanwhile, malignant lesions of the placenta are collectively called gestational trophoblastic |\n\n1Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK. 2Department of Microbiology, Trinity College, Dublin D02 VF25, Ireland.  \n*Authors for correspondence ([benjamin.schuster-boeckler@ludwig.ox.ac.uk](benjamin.schuster-boeckler@ludwig.ox.ac.uk); [nleathlm@tcd.ie](nleathlm@tcd.ie))  \n A. N. , 0000-0002-7318-9065; B.S.-B. , 0000-0002-8892-5133; M. N. L. , 0000- 0002-8523-4935  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0](https://creativecommons.org/licenses/by/4.0)), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.  \nneoplasia (GTN), which encompasses invasive moles, choriocarcinoma (CC), placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) (Fig. 1) (Ngan et al., 2021) . Although molar pregnancies can be treated by the removal of abnormal tissue (Sebire and Seckl, 2008), cancerous forms frequently require chemotherapy and/or hysterectomy and, in exceptionally rare cases, can metastasise to distal sites such as the brain, liver and lungs, leading to maternal death (Lurain, 2010) .  \nThe first reference to GTD dates to around 400 B.C., when Hippocrates described it as “drop","cbCaimYPuPVx2V14","https://ap.wps.com/l/cbCaimYPuPVx2V14","pdf",1098223,"English","# Introduction\n## Placental development and trophoblast-driven origin of GTD\n## Classification of benign GTD lesions\n## Classification of malignant GTD lesions\n## Historical context and clinical rationale","[{\"question\":\"What is gestational trophoblastic disease (GTD)?\",\"answer\":\"GTD is a group of rare benign and cancerous lesions arising from trophoblast cells of the placenta. These lesions can form abnormal molar tissue or progress to cancer.\"},{\"question\":\"How is GTD classified into benign and malignant forms?\",\"answer\":\"Benign GTD includes hydatidiform mole and atypical placental site nodule (APSN). Malignant forms are collectively termed gestational trophoblastic neoplasia (GTN), including invasive moles, choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumour (ETT).\"},{\"question\":\"Why is studying GTD at the molecular level important?\",\"answer\":\"Molecular study can improve understanding of pathogenesis and developmental origins, reduce misdiagnosis, and explain high responsiveness and treatment sensitivity. It may also help guide more effective therapeutic interventions and inform broader cancer research.\"}]","Gestational trophoblastic disease: understanding the molecular mechanisms of placental tumours | PDF",1790157478,25]