Department of Biomedical Sciences, Dong-A University, Busan, 49315, Korea.
Department of Health Sciences, The Graduated of Dong-A University, Busan, 49315, Korea.
BMC Med Genomics. 2021 May 5;14(1):121. doi: 10.1186/s12920-021-00968-1.
ABL1 is primarily known as a leukemia-related oncogene due to translocation, but about 2.2% of ABL1 mutations have been identified in bladder cancer, and high expression in solid cancer has also been detected.
Here, we used the NCBI database, UCSC genome browser gateway and Tandem repeat finder program to investigate the structural characterization of the ABL1 breakpoint region and to identify the variable number of tandem repeats (VNTR). To investigate the relationship between ABL1-MS1 and bladder cancer, a case-controlled study was conducted in 207 controls and 197 bladder cancer patients. We also examined the level of transcription of the reporter gene driven by the ABL1 promoter to determine if the VNTR region affects gene expression.
In our study, one VNTR was identified in the breakpoint region, the intron 1 region of ABL1, and was named ABL1-MS1. In the control group, only two common alleles (TR13, TR15) were detected, but an additional two rare alleles (TR14, TR16) were detected in bladder cancer. A statistically significant association was identified between the rare ABL1-MS1 allele and bladder cancer risk: P = 0.013. Investigating the level of transcription of the reporter gene driven by the ABL1 promoter, VNTR showed inhibition of ABL1 expression in non-cancer cells 293 T, but not in bladder cancer cells. In addition, ABL1-MS1 was accurately passed on to offspring according to Mendelian inheritance through meiosis.
Therefore, the ABL1-MS1 region can affect ABL1 expression of bladder cancer. This study provides that ABL1-MS1 can be used as a DNA fingerprinting marker. In addition, rare allele detection can predict susceptibility to bladder cancer.
ABL1 主要作为白血病相关的癌基因，由于易位而被发现，但约 2.2%的 ABL1 突变已在膀胱癌中被鉴定出来，并且在实体瘤中也检测到高表达。
在这里，我们使用 NCBI 数据库、UCSC 基因组浏览器网关和串联重复查找程序来研究 ABL1 断裂点区域的结构特征，并鉴定可变数目的串联重复（VNTR）。为了研究 ABL1-MS1 与膀胱癌之间的关系，我们在 207 名对照和 197 名膀胱癌患者中进行了病例对照研究。我们还检查了由 ABL1 启动子驱动的报告基因的转录水平，以确定 VNTR 区域是否影响基因表达。
在我们的研究中，在 ABL1 的内含子 1 区域的断裂点区域中鉴定出一个 VNTR，命名为 ABL1-MS1。在对照组中，仅检测到两个常见等位基因（TR13、TR15），但在膀胱癌中检测到另外两个罕见等位基因（TR14、TR16）。罕见的 ABL1-MS1 等位基因与膀胱癌风险之间存在统计学显著关联：P=0.013。研究报告基因由 ABL1 启动子驱动的转录水平，VNTR 显示在非癌细胞 293T 中抑制 ABL1 表达，但在膀胱癌细胞中没有。此外，ABL1-MS1 通过减数分裂按照孟德尔遗传规律准确传递给后代。
因此，ABL1-MS1 区域可以影响膀胱癌中 ABL1 的表达。本研究表明 ABL1-MS1 可作为 DNA 指纹标记物。此外，罕见等位基因的检测可以预测膀胱癌的易感性。
