What will be the effect of common essential genes in normal cells? Are they only essential for cancer cell lines?
We believe they are essential for (most) normal cells to proliferate. A gene that’s essential for successful proliferation might not be otherwise. We don’t currently distinguish between genes whose loss causes cell cycle arrest and those that cause cell death.
We could imagine a gene that’s essential in all cancer cells and only cancer cells. Such a gene would be the holy grail of targets for cell therapy. But it’s pretty unlikely to exist. If there really were such a “cancer essential” gene that wasn’t essential for normal cells, there would be strong evolutionary pressure to lose it and get whatever benefits it provides in some other way. Additionally, we know many different kinds of alterations can give rise to cancer, and even trees develop tumors. It’s hard to see how one gene could be essential in all the diverse routes to malignancy but not be important for normal cell function. However, due to the difficulties of screening normal tissue, we’ve never tested this directly.
Hello, I am new to Depmap and am slowly unravelling its usefulness in helping me with screening for novel gene candidates to work on. While I am aware that a negative CERES or DEMETER2 score corresponds to an essential gene in a cancer type, meaning if the gene is lost, the cancer cells will not survive, suggesting that it is a potential oncogene. Hence so I am wondering if a positive score would mean the opposite, i.e. the gene could serve as a potential tumor suppressor?
Yes, although one should be careful. Small positive scores are likely to be noise. Even large positive scores can be caused by the random outgrowth of individual clones. In general, we haven’t found CRISPR data to be as good for finding new tumor suppressors as it is for finding dependencies.