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

妊娠滋养细胞肿瘤（GTNs）包括一组由异常滋养细胞引起的妊娠相关肿瘤。恶性肿瘤包括侵袭性痣、绒毛膜癌和罕见的胎盘部位和上皮样滋养细胞肿瘤（PSTT和ETT），可能在病因正常或异常（如磨牙）妊娠后数月至数年才被诊断出来。与大多数GTN一样，在致病妊娠4年内诊断的PSTT和ETT是高度可治愈的（约98%），然而，在致病妊娠4年后诊断的PSTT/ETT病例即使采用更积极的现代治疗方法，死亡率也有50%。PSTT和ETT在分子水平上的特征都很差，迄今为止发表的基因组或转录组学研究很少。我们假设PSTT/ETT之间存在遗传或表观遗传差异，这些差异出现在致病妊娠后4年和40年。为了更好地了解长间隔和短间隔PSTT/ ts之间的分子差异，我们将对这些罕见肿瘤进行基因组学、转录组学和表观遗传学表征；识别这些差异将有助于改善患者分层和新的精准医学治疗。

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.