Genomic characterisation of gestational trophoblastic tumours and associated circulating tumour DNA to improve patient management and diagnosis

Gestational trophoblastic neoplasms (GTNs) comprise a group of pregnancy related tumours which arise from abnormal trophoblastic cells. The malignancies, which include invasive moles, choriocarcinoma, and the rarer placental site and epithelioid trophoblastic tumours (PSTT and ETT), may be diagnosed months to years after the causative normal or abnormal (e.g., molar) pregnancy. As is the case for most GTN, PSTT and ETTs diagnosed within 4 years of the causative pregnancy are highly curable (>98%), however PSTT/ETT cases diagnosed more than 4 years after the causative pregnancy have a 50% mortality rate, even with more aggressive modern therapies.

Both PSTT and ETT are poorly characterised at the molecular level, with very few genomic or transcriptomic investigations published to date. We hypothesise that there are genetic or epigenetic differences between PSTT/ETT that arise <4 and >4 years since the causative pregnancy. To gain a greater understanding of the molecular differences between long and short interval PSTT/ETTs we will conduct genomic, transcriptomic, and epigenetic characterisation of these rare tumours; identifying these differences should lead to improved patient stratification and new precision medicine-based therapies.