Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)—a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer – neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.

中文翻译：

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BARD1β同工型在部分小儿肿瘤中的表达

当前，正在搜索和测试许多新的可能的生物标志物和机制，以分析儿科肿瘤的病理生物学，以开发新的治疗方法。一种这样的候选分子因子是BARD1（与BRCA1相关的RING域1）—一种参与细胞周期控制和基因组稳定性的肿瘤抑制基因，参与多种类型的成年型肿瘤。关于BARD1在儿童癌症中的意义的数据有限。这项研究确定了BARD1的表达水平使用qPCR方法在三种不同的儿童癌症的组织遗传学组-成神经细胞瘤中，以及首次在选定的生殖细胞肿瘤（GCT）和横纹肌肉瘤（RMS）中发现其同工型（β）。我们发现，与健康组织相比，β亚型在肿瘤中的表达更高，而与BARD1全长无关。另外，观察到在神经母细胞瘤的组织学类型之间BARD1β表达的差异，在神经节神经母细胞瘤和神经节神经瘤中水平更高。此外，与非肿瘤组织相比，BARD1β表征卵黄囊肿瘤（GCT型）和RMS的表达更高。这些肿瘤还显示出TERT的高表达（端粒酶逆转录酶）基因。在两个RMS病例中，我们发现化疗后样品中BARD1β的深度降低。这项工作支持β同工型在小儿肿瘤中的致癌性，并证明其表达的差异取决于肿瘤的组织学类型和成神经细胞肿瘤的成熟水平。