Identifying structural variants, such as gene fusions, plays a crucial role in cancer genomics, as they can drive the development and progression of various cancers. Gene fusions, where parts of two different genes combine to form a new hybrid gene, are often a result of chromosomal rearrangements such as translocations, deletions, or inversions. These genetic alterations often lead to abnormal protein function that can significantly impact cellular processes promoting cancer cell growth and disease propagation. Understanding and identifying these events is essential for developing targeted therapies and improving diagnostic accuracy.
cBioPortal supports gene fusion data by providing visualizations and detailed annotations for these fusion events in the OncoPrint tab in the Results View. Users can identify which genes are involved in fusions across different cancer types and understand the frequency and distribution of these fusions in selected studies. The Onco Query Language (OQL) also supports querying for fusion events for a given gene across one or multiple studies. The basic OQL notation that exists in cBioPortal is as follows:
GeneID: FUSION
The above query searches for all reported gene fusion events for a gene across the selected study(ies). Let’s look at the result of such a query in the MSK-IMPACT Clinical Sequencing Cohort study in cBioPortal. In this study, the TMPRSS2 gene is most commonly found in structural variants in prostate cancer tumor samples. We first submit a query (TMPRSS2: FUSION) for all fusion events in the TMPRSS2 gene in prostate cancer.
Following the query above, we can see in the OncoPrint tab (Figure 1) that in 29% of the samples profiled for gene fusions, TMPRSS2 is fused with another gene in prostate cancer. However, using this simple query notation, the user is not immediately aware of the frequency of fusion events where TMPRSS2 is in the upstream/downstream regions of the fusion. The most frequent fusion partners are also only visible when hovering over the samples in the TMPRSS2: FUSION track. This was a limitation for users specifically interested in researching the fusion events. To answer the need for a more detailed look at gene fusion events in cBioPortal, our team at The Hyve has developed new OQL support functionalities.
A new way to query for gene fusions in cBioPortal
The new update to the OQL introduces a syntax to specify the orientations of any gene pair involved in the fusion event. These enhancements allow for a more precise and detailed exploration of fusion events. Table 1 summarizes the new syntax.
Now, let’s take another look at our example from before using the newly developed OQL support. To find fusions where TMPRSS2 is specifically the upstream or downstream gene we add “TMPRSS2::” and “::TMPRSS2” to our query, respectively. Modifying the query, we see two new tracks added to the OncoPrint tab for the specific fusion events. The results make it clear that the TMPRSS2 gene is more often found in the downstream position of the gene fusion events (Figure 2).
How about other genes involved in fusion events with TMPRSS2? In prostate cancer, ERG:TMPRSS2 fusion has been identified as a potential predictive marker [1]. Using the new OQL support developed by The Hyve, we can easily query for fusion events involving these two genes in a specific order. For fusions where ERG is the downstream gene, we add “TMPRSS2::ERG” and for fusions where TMPRSS2 is the downstream gene, we add “ERG::TMPRSS2” to our query.
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