Dear DepMap team,
We have been working with the fusion dataset (25Q3) and are interested in your thoughts about relevant oncogenic fusions for cancer cell lines. For example, several cell lines have well known oncogenic ALK fusions, such as NPM1-ALK /EML4-ALK, that are also sensitive to ALK inhibitors (Figure). This indicates that the ALK fusions are likely to drive the cell growth of these cell lines. However, there are also some cell lines that have an ALK fusion and that are not sensitive to ALK inhibitors. An example is the cell line KLE for which a BABAM2-ALK fusion is reported in DepMap. This fusion has a confidence level ‘high’ (called by Arriba) and is indicated as ‘likely oncogenic’ by oncoKB, but KLE does not show sensitivity for alectinib (Figure). Although it’s possible that this fusion is not driving the cell growth or that this specific fusion is not inhibited by alectinib, we wonder whether this fusion might be a false positive or only present in a small subset of KLE cells. Especially the FFPM, total reads supporting the fusion, and total fusion coverage are highly divergent between alectinib-sensitive cell lines and alectinib-insensitive cell lines (Table).
Do you have thoughts about possible thresholds and other methods to only include relevant oncogenic fusions?
Thanks in advance!
Daphne
Figure:
Table:
