The story of the oncogenes present in the SUM-159 cell line is interesting for several reasons. First, while it is quite common for breast cancer cells to exhibit copy number gains in the 8q24 region of the genome, these gains are almost always broad low-level gains that span a large segment of the 8q arm. As a result, these gains result in low level gains of the MYC gene. In contrast, SUM-159 cells exhibit a highly focal amplification of 8q24 that involves only the MYC gene resulting in high level amplification and over expression of the gene. In addition, SUM-159 cells have a point mutation in the HRAS gene! Amplification and overexpression of C-MYC coupled with a point mutation in HRAS….no wonder these cells looked like transformed fibroblasts. If that weren’t enough, these cells also have a recurrent PIK3CA point mutation. Interestingly, none of these driving oncogenes were hits in our functional shRNA screen although all three were close to our arbitrary cut point. This finding emphasizes the fact that one uses screen data with caution as both false positive and false negative results are possible. Indeed, we biased our analysis to limit false positive calls and as a result, some driving oncogenes with good scores still fall outside of our window for calling a gene a hit in the screen.
Here is the Candidate Oncogene Signature for SUM-159 cells
Note that because none of the oncogenes were screen hits, nor were any other genomically altered genes hits in the screen, there is only one Oncogene Signature for this cell line.
| GeneSymbol | DnaAmp | LogFoldChange | Mutation | OccurencesInCOSMIC | oncogene |
| MYC | 4.0248 | 1.207 | NULL | 0 | 1 |
| HRAS | NULL | -0.932 | HRASp.G12D | 48 | 1 |
| PIK3CA | NULL | -1.27 | PIK3CAp.H1047L | 249 | 1 |
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