Table 1. Proliferation-relevant sarcoma genes.
Transcriptional profiling of genetically engineered, KRAS-induced mouse rhabdomyosarcomas (RMS) and non-myogenic sarcomas (NMS) identified 141 sarcoma-relevant genes; their function was evaluated using a customized shRBA screen. Sixteen of the 141 sarcoma-relevant genes scored as „hits”in RMS and/ or NMS (p<0,01, q>0,05, at least 3 of 5 shRNAs with FDR< 30%) and are listed here. These 16 hits include 5 potentially druggable targets, i.e. Asns, Cenpe, Crebl2, HAs2 and Ube2c.
Kras; p16p19null RMS | Kras; p16p19null NMS | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Symbol | Cell function | Chemical modulation | Mean % of ctrl | Level | p-value | q value | Mean % of ctrl | Level | p-value | q value |
Asns | Asparagine synthesis | AS5, Asparaginase, Mupirocin | 30,16 | 2 | < .0001 | 0,0058 | 6,6934 | 1 | < .0001 | 0,0072 |
Rbbp8 | Cell cycle | 56,06 | 3 | 0,0022 | 0,0160 | 30,7323 | 2 | 0,0012 | 0,0288 | |
Rad54l | DNA repair | 57,56 | 3 | 0,0031 | 0,0180 | 40,5093 | 3 | 0,0076 | 0,0421 | |
Ube2c | Cell cycle | Bortezomib | 43,56 | 3 | < .0001 | 0,0058 | 38,6873 | - | 0,0054 | 0,0389 |
Cenpe | Chromosome stability | UA62784, GSK923295A | 72,49 | - | 0,0511 | 0,0689 | 39,9054 | 3 | 0,0067 | 0,0402 |
Has2 | Extracellular matrix | Latrunculin A | 61,76 | - | 0,0075 | 0,0335 | 41,5132 | 3 | 0,0088 | 0,0453 |
Creb3l2 | Transcriptional regulation | Sorafenib | 62,69 | 2 | 0,0090 | 0,0326 | 60,2497 | - | 0,1230 | 0,1736 |
Basp1 | Transcriptional regulation | 45,37 | 3 | 0,0002 | 0,0039 | 50,8361 | - | 0,0371 | 0,0989 | |
Lrrfip1 | Transcriptional regulation | 54,80 | 3 | 0,0017 | 0,0164 | 54,4497 | - | 0,0606 | 0,1322 | |
Lasp1 | Cytoskeletal organization | 60,37 | 3 | 0,0056 | 0,0271 | 58,6252 | 3 | 0,1019 | 0,1706 | |
Pold3 | DNA repair | 62,96 | 3 | 0,0095 | 0,0290 | 31,9654 | - | 0,0015 | 0,0216 | |
Efhd2 | Apoptosis | 53,27 | - | 0,0034 | 0,0179 | 46,8886 | 2 | 0,0007 | 0,0252 | |
Myo9b | Cytoskeletal organization | 67,41 | - | 0,0445 | 0,0737 | 33,5929 | 2 | 0,0021 | 0,0252 | |
Runx1 | Transcriptional regulation | 64,64 | - | 0,0455 | 0,0713 | 30,6930 | 3 | 0,0012 | 0,0288 | |
Shcbp1 | Cell proliferation | 71,42 | - | 0,1118 | 0,1099 | 37,7316 | 3 | 0,0045 | 0,0405 | |
Egr2 | Transcriptional regulation | 74,44 | - | 0,0689 | 0,0850 | 42,9416 | 3 | 0,0048 | 0,0384 |