Genetic Basis of Gestational Trophoblastic Disease

Part of the Current Clinical Pathology book series (CCPATH)


Related to various trophoblastic cells within the placenta, gestational trophoblastic disease (GTD) consists of a distinct group of proliferative disorders that have unique clinical settings, genetic compositions, and varying biological behaviors. Recent laboratory investigations of biomarker expressions have delineated the cellular pathways of differentiation related to each of the entities of GTDs (Int J Gynecol Pathol 20(1):31–47, 2001). The most common hydatidiform moles are proliferative lesions of cells recapitulating chorionic villous trophoblasts. The most virulent gestational choriocarcinoma is a fully malignant tumor with proliferating cells recapitulating previllous trophoblasts of the developing placenta. The lesional cells of placental site trophoblastic tumor (PSTT) and exaggerated placental site reaction have cytological features resembling intermediate trophoblasts at the implantation site, whereas epithelioid trophoblastic tumor (ETT) and placental site nodule have proliferating cells resembling intermediate trophoblasts at the chorionic laeve. Biologically, the androgenetic nature of hydatidiform moles clearly indicates that an excessive paternal genome plays an important role in the development of these conditions, likely through an altered genomic imprinting. Recent linkage studies identified mutations of NALP7 on 19q13.4 as causal events in the development of familial biparental complete hydatidiform. Follow-up investigations into the biological aspects of NALP7 gene alterations may hold the key to unlock the mystery as how altered genomic imprinting and related gene expression result in the phenotype of diandric hydatidiform mole in general. Recent findings of the preferential requirement of a paternal X chromosome by several trophoblastic tumors suggest a unique genetic factor that may render a growth advantage to trophoblast in these tumors.


Genetic basis of GTD Genomic imprinting of GTD 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PathologyYale University School of MedicineNew HavenUSA

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