Sahu Dinesh Kumar, Singh Neetu, Das Mumani, Rawat Jiledar, Gupta Devendra Kumar
Molecular Biology Unit, Center for Advance Research, King George's Medical University, Lucknow, India.
Postgraduate Institute of Child Health, Noida, India.
Pediatr Surg Int. 2022 Nov;38(11):1601-1617. doi: 10.1007/s00383-022-05202-2. Epub 2022 Sep 15.
Wilms' tumor is the most-frequent malignant-kidney tumor in children under 3-4 years of age and is caused by genetic alterations of oncogenes (OG) and tumor-suppressor genes (TG). Wilms' tumor has been linked to many OG-&-TG. However, only WT1 has a proven role in the development of this embryonic-tumor.
The study investigates the level of mRNA expression of 16 OGs and 20 TGs involved in key-signaling pathways, including chromatin modification; RAS; APC; Cell Cycle/Apoptosis; Transcriptional Regulation; PI3K; NOTCH-&-HH; PI3K & RAS of 24-fresh Wilms'-tumor cases by capture-and-reporter probe Code-Sets chemistry, as CNVs in these pathway genes have been reported.
Upon extensively investigating, MEN1, MLL2, MLL3, PBRM1, PRDM1, SMARCB1, SETD2, WT1, PTPN11, KRAS, HRAS, NF1, APC, RB1, FUBP1, BCOR, U2AF1, PIK3CA, PTEN, EBXW7, SMO, ALK, CBL, EP300-and-GATA1 were found to be significantly up-regulated in 58.34, 62.5, 79.17, 91.67, 58, 66.66,54, 58.34, 66.67, 75, 62.5, 62.5, 58, 79.17, 79.17, 75, 70.84, 50, 50, 75, 66.66, 62.50, 61.66, 58.34-and-62.50% of cases respectively, whereas BRAF, NF2, CDH1, BCL2, FGFR3, ERBB2, MET, RET, EGFR-and-GATA2 were significantly down regulated in 58, 87.50, 79.16, 54.16, 79.17, 91.66, 66.66, 58.33, 91.66-and-62.50% of cases, respectively. Interestingly, the WT1 gene was five-fold down regulated in 41.66% of cases only.
Hence, extensive profiling of OGs and TGs association of major-signaling pathways in Wilms' tumor cases may aid in disease diagnosis. PBRM1 (up-regulated in 91.67% of cases), ERBB2 and EGFR (down-regulated in 91.66 and 91.66% of cases, respectively) could be marker genes. However, validation of all relevant results in a larger number of samples is required.
肾母细胞瘤是3 - 4岁以下儿童中最常见的恶性肾肿瘤，由癌基因（OG）和肿瘤抑制基因（TG）的基因改变引起。肾母细胞瘤与许多OG和TG有关。然而，只有WT1在这种胚胎肿瘤的发生发展中具有已被证实的作用。
本研究通过捕获和报告探针编码集化学方法，研究了24例新鲜肾母细胞瘤病例中参与关键信号通路的16个OG和20个TG的mRNA表达水平，这些信号通路包括染色质修饰、RAS、APC、细胞周期/凋亡、转录调控、PI3K、NOTCH和HH、PI3K和RAS，因为这些通路基因中的拷贝数变异（CNV）已有报道。
经过广泛研究发现，MEN1、MLL2、MLL3、PBRM1、PRDM1、SMARCB1、SETD2、WT1、PTPN11、KRAS、HRAS、NF1、APC、RB1、FUBP1、BCOR、U2AF1、PIK3CA、PTEN、EBXW7、SMO、ALK、CBL、EP300和GATA1在病例中的上调率分别为58.34%、62.5%、79.17%、91.67%、58%、66.66%、54%、58.34%、66.67%、75%、62.5%、62.5%、58%、79.17%、79.17%、75%、70.84%、50%、50%、75%、66.66%、62.50%、61.66%、58.34%和62.50%，而BRAF、NF2、CDH1、BCL2、FGFR3、ERBB2、MET、RET、EGFR和GATA2在病例中的下调率分别为58%、87.50%、79.16%、54.16%、79.17%、91.66%、66.66%、58.33%、91.66%和62.50%。有趣的是，WT1基因仅在41.66%的病例中下调了5倍。
因此，对肾母细胞瘤病例中主要信号通路的OG和TG关联进行广泛分析可能有助于疾病诊断。PBRM1（在91.67%的病例中上调）、ERBB2和EGFR（分别在91.66%和91.66%的病例中下调）可能是标记基因。然而，需要在更多样本中验证所有相关结果。
