Table 1 Capacity of TMIM screens to identify common human cancer genes in three cancer typesa
From: The utility of transposon mutagenesis for cancer studies in the era of genome editing
Cancer type | Genes commonly mutated in human cancer | Recurrent genes identified by TMIM screens | Comments | Novel, functionally validated cancer genes identified in TMIM screens |
|---|---|---|---|---|
Colorectal | APC [102] | Â | CNOT1, PDE4DIP, PDCD6IP, ATF2, SFI1 [22] | |
| Â | TP53 [102] | Tp53 has been rarely targeted in any TMIM screen, although upstream regulators such as Cdkn2a are frequently targeted in TMIM screens | ||
ANKRD11, CSNK2A1, MKL2, MYO9A, RNF43, SIN3A, Zfp292 [51] | ||||
| Â | KRAS [102] | Insertions in Kras have been detected at low frequency in Apc-deficient backgrounds [23], perhaps reflecting the inability of transposons to cause point mutations in target genes through insertion alone. However, upstream and downstream genes within the Kras signaling pathway are targeted in TMIM screens, leading to pathway activation | ||
| Â | PIK3CA [102] | No | Other phosphoinositide 3-kinase pathway genes have been targeted, for example Pik3r1 and Pten | |
| Â | FBXW7 [102] | Â | ||
| Â | SMAD4 [102] | Â | ||
| Â | CTNNB1 [102] | Â | ||
| Â | NRAS [102] | No | Recurrent insertions in Nras have not been found, probably owing to the same reasons applicable to Kras | |
| Â | TCF7L2 [102] | Â | ||
|  | FAM123B [102] | No | Other components of Wnt–β-catenin pathway are targeted in tumors, for example Apc and Ctnnb1. | |
Melanoma | Yes [49] | Identified as potential mediator of BRAF inhibitor resistance | ERAS [49] | |
| Â | No | Â | ||
| Â | No | Â | CEP350 [38] | |
| Â | Â | MAGI2, PTPRO, Map3k1 [57] | ||
| Â | Â | |||
| Â | Yes [38] | Melanoma TMIM screens were performed in a Braf-mutant background. NF1 mutations are typically mutually exclusive from BRAF mutations in human melanoma, potentially accounting for the lack of Nf1 insertions in some screens | ||
| Â | No | Other genes operating in Rho GTPase pathways have been targeted | ||
| Â | No | Other MAP kinase pathway genes have been targeted in melanoma TMIM screens | ||
| Â | No | Â | ||
| Â | Identified as potential mediator of BRAF inhibitor resistance | |||
Pancreatic | Yes (low frequency) [24] | Pancreatic cancer TMIM screens were performed in a Kras G12D background | USP9X [24] | |
| Â | No | Recurrent insertions in Tp53 were not observed despite the high prevalence of TP53 alterations in human pancreatic cancer. Cdkn2a was a recurrent CIS-associated gene, and Usp7, a p53-regulatory deubiquitinase, was targeted at low frequency in one study [24] | Foxp1, Foxp2, Bcl6, Fign [32] | |
| Â | Â | |||
| Â | Â | |||
| Â | PREX2 [106] | No | Â | |
| Â | Â | |||
| Â | RNF43 [106] | Â | ||
| Â | KDM6A [106] | Â | ||
| Â | Â | |||
| Â | MLL3 [105] | Â |