WT‐CLS1 is a rhabdoid tumor cell line and can be inhibited by miR‐16

Abstract

Background: Wilms tumor and rhabdoid tumor can have similar clinical presentations, but they have distinct histological and biological features. For instance, Wilms tumors commonly bear mutations in kidney differentiation or microRNA processing genes, whereas rhabdoid tumor is characterized by loss of SMARCB1. Aims:We initially set out to characterize and identify tumor suppressor microRNAs in WT-CLS1, which had been described as a Wilms tumor cell line. Methods and Results:We characterized the cell line WT-CLS1 by whole exome sequencing, RNA-seq, and xenograft histology. We measured the effect of microRNA overexpression on WiT49, WT-CLS1, BT-12, and CHLA-06-ATRT.We found that miR-16 significantly impairs cell proliferation in WT-CLS1 by repressing numerous cell cycle genes, including the D-type cyclins. In addition, we found that the WT-CLS1 cell line demonstrates the classic histological, mutational, and transcriptional hallmarks of rhabdoid tumor, including SMARCB1 loss. Lastly, miR-16 also represses cell cycle genes and impairs proliferation in the BT-12 and CHLA-06-ATRT rhabdoid tumor cell lines. Conclusions:The loss of SMARCB1 warrants reclassification of WT-CLS1 as rhabdoid tumor. Overexpression of miR-16 significantly abrogates proliferation of WT-CLS1 and other rhabdoid tumor cell lines. Further studies are necessary to gain insight into the potential for miR-16 to be a tumor suppressor or a novel therapeutic in rhabdoid tumor. KEYWORDS miR-16, rhabdoid tumor, WT-CLS1Abbreviations: ATRT, atypical teratoid/rhabdoid tumor; CDK4, cyclin-dependent kinase 4; EZH2, Enhancer of zeste homolog 2; miRNA, microRNA; SWI/SNF, Switch/ sucrose non-fermentable

Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor

“…The development and testing of preclinical therapies focusing on these key groups of WT patients have been limited by the paucity of available relevant in vitro and in vivo WT models 17 . The one commercially available, purported WT cell line (WT-CLS1) was recently reclassified as a malignant rhabdoid tumor due to presence of hemizygous SMARCB1 mutation 18 . The G401 cell line was also previously reclassified as a rhabdoid tumor line 19,20 .…”

Retinoic acid promotes differentiation of WiT49‐ but not of CCG99‐11 Wilms tumour cells

“…Especially since over the years some of them have been re-evaluated and been designated as other tumour entities based on for instance their genetic profiles. [26][27][28] Tumour genetics could also explain why the two cell lines respond differently. SIX2 is recurrently mutated in Wilms tumour, but mutations in the gene do not seem to affect SIX2 protein expression according to the literature.…”

Prohibitin is a prognostic marker and therapeutic target to block chemotherapy resistance in Wilms’ tumor

“…(F) A receiver-operating characteristic curve demonstrates the prognostic power of diagnostic urine prohibitin to predict abdominal relapse in favorable-histology Wilms' tumor at different sensitivity and specificity with an AUC of 0.96 (95% CI, 0.91-1.0). tumor of the kidney due to the presence of disease-defining SMARCB1 mutation (20). Using quantitative fluorescent Western blot immunoassays, we found that PHB is more highly expressed in renal tumor cell lines, as compared with BJ fibroblasts ( Figure 4A).…”