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（GTN）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、绒毛膜癌和更罕见的胎盘部位和上皮样滋养细胞肿瘤（PSTT和ETT），可以在病因正常或异常（例如，摩尔）怀孕。与大多数GTN一样，在病因妊娠4年内诊断的PSTT和ETT是高度可治愈的（>98%），然而，在病因妊娠4年后诊断的PSTT/ETT病例即使采用更积极的现代治疗，死亡率也高达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，这些差异自<4 and >病因妊娠4年后出现。为了更好地了解长间期和短间期PSTT/ETTs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;识别这些差异应有助于改善患者分层和新的精确药物治疗。

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.