Goodspeed Andrew, Bodlak Avery, Duffy Alexis B, Nelson-Taylor Sarah, Oike Naoki, Porfilio Timothy, Shirai Ryota, Walker Deandra, Treece Amy, Black Jennifer, Donaldson Nathan, Cost Carrye, Garrington Tim, Greffe Brian, Luna-Fineman Sandra, Demedis Jenna, Lake Jessica, Danis Etienne, Verneris Michael, Adams Daniel L, Hayashi Masanori
bioRxiv. 2024 Jun 20:2024.01.18.576251. doi: 10.1101/2024.01.18.576251.
Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.
尤因肉瘤是儿童中第二常见的骨癌，占儿童癌症诊断病例的2%。与局限性疾病患者超过70%的5年生存率相比，诊断时出现转移性疾病的患者预后很差。在这里，我们利用单细胞RNA测序来表征原发性尤因肉瘤肿瘤及其周围肿瘤微环境（TME）的转录图谱。拷贝数分析确定了治疗前患者体内的亚克隆进化。原发性肿瘤样本表现出异质性的转录图谱，具有几个保守的基因表达程序，包括那些由与增殖和EWS靶点相关的基因组成的程序。诊断时循环肿瘤细胞的单细胞RNA测序和免疫荧光确定TSPAN8为一个新的治疗靶点。
