Abstract
Several fusion genes are directly involved in the initiation and progression of cancers. Numerous bioinformatics tools have been developed to detect fusion events, but they are mainly based on RNA-seq data. The whole-exome sequencing (WES) represents a powerful technology that is widely used for disease-related DNA variant detection. In this study, we build a novel analysis pipeline called Fuseq-WES to detect fusion genes at DNA level based on the WES data. The same method applies also for targeted panel sequencing data. We assess the method to real datasets of acute myeloid leukemia (AML) and prostate cancer patients. The result shows that two of the main AML fusion genes discovered in RNA-seq data, PML-RARA and CBFB-MYH11, are detected in the WES data in 36 and 63% of the available samples, respectively. For the targeted deep-sequencing of prostate cancer patients, detection of the TMPRSS2-ERG fusion, which is the most frequent chimeric alteration in prostate cancer, is 91% concordant with a manually curated procedure based on four other methods. In summary, the overall results indicate that it is challenging to detect fusion genes in WES data with a standard coverage of ∼ 15–30x, where fusion candidates discovered in the RNA-seq data are often not detected in the WES data and vice versa. A subsampling study of the prostate data suggests that a coverage of at least 75x is necessary to achieve high accuracy.
Highlights
Fusion genes represent an important class of genomic alteration contributing to the tumorigenesis for both solid and hematological cancers
In the early 1980s, the first fusion gene was discovered in patients with chronic myeloid leukemia (CML), which was caused by the translocation between chromosome 9 and 22
We aim to exploit the potential value of whole exome sequencing data in the context of fusion gene detection
Summary
Fusion genes represent an important class of genomic alteration contributing to the tumorigenesis for both solid and hematological cancers. The hybrid genes are often produced by recurrent chromosomal rearrangements, such as translocation, deletion and insertion (De Braekeleer et al, 2011; Sonoda et al, 2018; Suo et al, 2018). In the early 1980s, the first fusion gene was discovered in patients with chronic myeloid leukemia (CML), which was caused by the translocation between chromosome 9 and 22. The fusion gene, BCR-ABL1, plays a prominent role in inducing the chronic myeloid leukemia (Chandran et al, 2019). A great number of fusion genes with functional impacts have been detected in different cancers. In the high-grade serous ovarian cancer, about 7% of patients carrying the BCAM-AKT2 fusion, which is specific and unique for this cancer type
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