Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models [SNP array]

Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages. Genomic DNA extracted from testicular cancer PDX tumors was genotyped using the Infinium Global Screening Array-24 v1.0 BeadChip (Illumina) with extra custom content. 10 samples

睾丸癌（Testicular cancer, TC）是年轻男性最常见的实体瘤。尽管基于顺铂的化疗对睾丸癌患者具有显著疗效，但化疗耐药仍导致10%的疾病相关死亡。目前亟需能够真实复刻患者肿瘤生物学特征的临床前模型，以助力靶点发现与药物研发。研究人员将8名睾丸癌患者的肿瘤组织皮下移植至NOD-scid-γ（NSG）免疫缺陷小鼠体内，成功构建3株睾丸癌患者来源异种移植（Patient-derived xenograft, PDX）模型，其中1株为化疗耐药模型，该模型包含卵黄囊瘤与畸胎瘤组分。对这些TP53野生型的PDX肿瘤开展全外显子测序、拷贝数变异分析与RNA测序，以评估传代对肿瘤分子特征的影响，结果显示不同传代肿瘤的分子特征具有高度一致性。研究人员采用Infinium全球筛查芯片-24 v1.0微珠芯片（Illumina）及额外定制内容，对从睾丸癌PDX肿瘤中提取的基因组DNA进行基因分型，共纳入10份样本。