Department of Biology and Medical Genetics, Medical University of Gdansk, 1 Debinki St., 80-211 Gdansk, Poland.
Laboratory of Clinical Genetics, University Clinical Centre, 17 Smoluchowskiego St., 80-210 Gdansk, Poland.
Genes (Basel). 2021 Jan 26;12(2):168. doi: 10.3390/genes12020168.
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 (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 significance in childhood cancer is limited. This study determines the expression level of 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 full-length. Additionally, differences in expression of β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the (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.
目前,许多新的可能的生物标志物和机制正在被寻找和测试,以分析儿科肿瘤的病理生物学,为新的治疗方法的发展提供依据。这样的候选分子因素之一是(BRCA1 相关 RING 结构域 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,参与多种成人型肿瘤。关于其在儿童癌症中的意义的数据有限。本研究使用 qPCR 方法,在三种不同组织发生的儿科肿瘤-神经母细胞瘤和生殖细胞肿瘤(GCT)和横纹肌肉瘤(RMS)中,首次确定了 及其同工型β(β)的表达水平。我们发现肿瘤中β同工型的表达高于健康组织,而全长的表达没有变化。此外,还观察到神经母细胞瘤不同组织类型之间β表达的差异,神经母细胞瘤和神经节细胞瘤的水平较高。此外,与非肿瘤组织相比,卵黄囊肿瘤(GCT 型)和 RMS 中β 的表达水平更高。这些肿瘤还表现出高的端粒酶逆转录酶(Telomerase Reverse Transcriptase)基因表达。在两个 RMS 病例中,我们发现化疗后样本中 BARD1β的深度降低。这项工作支持β同工型在儿科肿瘤中的致癌性,同时也表明其表达水平取决于肿瘤的组织学类型,以及神经母细胞瘤的成熟程度。