Table 1.
Gene name | Predicted functional effect of insertions | No. of distinct insertion sites | No. of independent transfections with insertions | Total no. of clones with insertions |
MET | Activating | 19 | 12 | 129 |
YES1 | Activating | 15 | 8 | 109 |
FYN | Activating | 14 | 9 | 30 |
GSK3B | Inactivating | 7 | 4 | 8 |
SOS1 | Activating | 6 | 12 | 37 |
DNM3 | Inactivating | 4 | 8 | 24 |
NAV2 | Inactivating | 4 | 5 | 15 |
EPS8 | Activating | 4 | 2 | 6 |
KRAS | Activating | 4 | 2 | 5 |
MYOF | Inactivating | 3 | 4 | 19 |
RABGAP1L | Activating | 3 | 3 | 15 |
RAF1 | Activating | 3 | 3 | 6 |
RABGAP1 | Activating | 3 | 3 | 4 |
Candidate genes from a transposon mutagenesis screen for resistance to afatinib in the EGFR-mutant PC9 lung adenocarcinoma cell line. A total of 1,927 distinct transposon insertion sites were identified in 188 afatinib-resistant PC9 clones from 13 independent transfections. Insertions were predicted to be activating if a transposon was situated near the transcription start site or first intron of a known human gene and was correctly oriented to drive expression of that gene. Genes that were found to be disrupted by insertions in both orientations or throughout the body of the gene were predicted to be inactivated.