Azatyan Ani, Zaphiropoulos Peter G
Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.
Cancers (Basel). 2022 Jun 26;14(13):3134. doi: 10.3390/cancers14133134.
The cerebellar cancer medulloblastoma is the most common childhood cancer in the brain. . RNA sequencing of 81 human biospecimens of medulloblastoma using pipelines to detect circular and fusion RNAs. Validation via PCR and Sanger sequencing. 27, 56, 28 and 11 RNA circles were found to be uniquely up-regulated, while 149, 7, 20 and 15 uniquely down-regulated in the SHH, WNT, Group 3, and Group 4 medulloblastoma subtypes, respectively. Moreover, linear and circular fusion RNAs containing exons from distinct genes joined at canonical splice sites were also identified. These were generally expressed less than the circular RNAs, however the expression of both the linear and the circular fusions was comparable. Importantly, the expression of the fusions in medulloblastoma was also comparable to that of cerebellum. A significant number of fusions in tumor may be generated by mechanisms similar to the ones generating fusions in normal tissue. Some fusions could be rationalized by read-through transcription of two neighboring genes. However, for other fusions, e.g., a linear fusion with an exon from a downstream gene joined 5' to 3' with an exon from an upstream gene, more complicated splicing mechanisms, e.g., trans-splicing, have to be postulated.
小脑癌髓母细胞瘤是儿童最常见的脑癌。使用检测环状和融合RNA的流程对81份人类髓母细胞瘤生物样本进行RNA测序。通过聚合酶链反应（PCR）和桑格测序进行验证。在SHH、WNT、3组和4组髓母细胞瘤亚型中，分别发现27、56、28和11个RNA环独特地上调，而149、7、20和15个RNA环独特地下调。此外，还鉴定出了在典型剪接位点连接不同基因外显子的线性和环状融合RNA。这些通常比环状RNA表达量少，然而线性和环状融合RNA的表达量相当。重要的是，髓母细胞瘤中融合RNA的表达与小脑的表达也相当。肿瘤中大量的融合RNA可能是由与正常组织中产生融合RNA类似的机制产生的。一些融合RNA可以通过两个相邻基因的通读转录来解释。然而，对于其他融合RNA，例如一个下游基因的外显子与一个上游基因的外显子从5'到3'连接的线性融合RNA，则必须假定存在更复杂的剪接机制，如反式剪接。
