Figure 2.

Approaches to generating matched cell lines for synthetic lethality screens. There are multiple approaches to generate matched cell lines if a loss of function (A-C) or a gain of function (D-F) of a specific gene is studied. For studying synthetic lethal interactions in cancer cells that have lost expression of a gene: A) the cDNA for the gene can be re-expressed in the deficient cell line; B) multiple cancer lines both expressing and deficient in the gene can be investigated; or C) cancer lines that express the gene can be treated to inactivate the gene. For studying synthetic lethal interactions in cancer cells with oncogenic mutations that increase activity of the gene or create a new gene fusion (like BCR-ABL), multiple approaches can be used: D) cells can be treated with RNAi or a chemical inhibitor in order to reduce the expression back to or below normal levels; E) multiple cancer lines both with and without the mutation could be investigated; or F) the activating mutation can be introduced or the gene can be overexpressed within a cancer line that has normal expression of WT gene.