Table 1.
Comparative analysis of confirmed and non-confirmed fusion structural and expression features.
| Sample ID | Fusion Type (5′-3′) | ORF Preserved (Yes/No) 1 | TK Domain Retained (Yes/No) 2 | RTK on 5′/3′ End | Presence in Fusion DBs 3 | Greater RTK Downstream Reads (Yes/No) 4 | Expr. of 5′/3′ Moieties 5 | N Reads 6 |
|---|---|---|---|---|---|---|---|---|
| Experimentally confirmed RTK fusions | ||||||||
| AL-98 | BCR-ABL1 | Yes | Yes | 3′ | Yes | Yes | 1.02/0.47 | 1 |
| FS-1 | CCDC6-RET | Yes | Yes | 3′ | Yes | Yes | 0.4/0.35 | 3 |
| LuC-46 | SLC34A2-ROS1 variant 1 | Yes | Yes | 3′ | Yes | Yes | 24.53/5.29 | 1 |
| LuC-46 | SLC34A2-ROS1 variant 2 | Yes | Yes | 3′ | Yes | Yes | 23.29/6.09 | 5 |
| LuC-46 | SLC34A2-ROS1 variant 3 | Yes | Yes | 3′ | Yes | Yes | 23.29/5.87 | 4 |
| LuC-46 | SLC34A2-ROS1 variant 4 | No | Yes | 3′ | Yes | Yes | 23.29/5.93 | 1 |
| OC-11 | FGFR2-LGSN | Yes | Yes | 5′ | No * | ND | 0.72/0.43 | 6 |
| OC-11 | RPS24-FGFR2 | Yes | No | 3′ | No | No | 5.74/0.29 | 5 |
| BC-105 | FBXL20-ERBB2 | No | Yes | 3′ | Yes | Yes | 1.28/11.77 | 18 |
| BC-105 | ATP2B1-ERBB2 | Yes | Yes | 3′ | No | No | 0.41/12.41 | 8 |
| Experimentally non-confirmed RTK fusions | ||||||||
| GC-30 | ABL1-ALDH1A2 | Yes | No | 5′ | No | ND | 0.04/0.43 | 1 |
| LuC-71 | NTRK2-AL157886.1 | No | No | 5′ | No | ND | NA | 1 |
| LuC-11 | KIF27-NTRK2 | Yes | Yes | 3′ | No | No | 0.02/0.67 | 1 |
| LuC-19 | NTRK2-USP47 | No | No | 5′ | No | ND | 0.83/0.24 | 1 |
| LuC-81 | ETNK1-NTRK2 | No | No | 5′ | No | ND | 0.22/6.36 | 1 |
| XC-1 | FGFR2-NFYC | No | No | 5′ | No | ND | 0.33/0.31 | 1 |
| OC-15 | ABL1-FNIP2 | Yes | No | 5′ | No | ND | 0.45/0.8 | 1 |
| AL-44 | FGFR1-AZIN1 | No | No | 5′ | No | ND | 0.15/0.6 | 1 |
| AL-7 | RET-GART | No | No | 5′ | No | ND | 0.016/0.48 | 1 |
| J1 | RBM18-ABL1 | No | No | 3′ | No | No | 1.94/1.9 | 1 |
| A549 | FGFR1-BRF1 | Yes | No | 5′ | No | ND | 1.21/0.52 | 1 |
| SkC-1 | ABL1-CD59 | No | No | 5′ | No | ND | 0.05/3.58 | 1 |
| BC-59 | FGFR1-REPS2 | No | No | 5′ | No | ND | 0.55/1.5 | 1 |
| EpS-1 | HMBOX1-FGFR1 | No | No | 3′ | No | No | 0.34/5.89 | 1 |
| PC-24 | DOCK1-FGFR2 | Yes | Yes | 3′ | No | No | 0.12/0.023 | 1 |
| Overall specificity | All confirmed vs. non-confirmed | 0.67 | 0.87 | NA | 1 | 1 | NA | 1 (1/>1) |
| Overall sensitivity | All confirmed vs. non-confirmed | 0.8 | 0.9 | NA | 0.7 | 0.78 | NA | 0.7 (1/>1) |
| Putative RTK fusions that were not experimentally investigated by RT-PCR | ||||||||
| TC-123 | NTRK2-MLPH | No | No | 5′ | No | ND | 0.97/0.22 | 1 |
| N-63 | CNTNAP3-NTRK2 | No | No | 3′ | No | Yes | 0.88/0.24 | 8 |
| RAIR-4 | NCOA4-RET | Yes | Yes | 3′ | Yes | Yes | 0.69/0.11 | 1 |
| TC-32 | NTRK2-IARS1 | Yes | No | 5′ | No | ND | 2.55/0.74 | 1 |
| TC-12 | ARHGAP12-ALK | No | Yes | 3′ | No | Yes | 0.46/0.02 | 1 |
| BT-24 | NTRK2-ADAM32 | Yes | Yes | 5′ | No | ND | 0.23/0.006 | 1 |
| BC-47 | FGFR2-RET | Yes | Yes | both | No | No | 0.06/1.36 | 1 |
| FFPE_4-2 | ZNF135-FGFR2 | Yes | Yes | 3′ | No | No | 0.06/0.46 | 1 |
| AL-84 | AGRN-FGFR3 | No | Yes | 3′ | No | Yes | 0.82/0.17 | 1 |
| FFPE-5 | AC016907.2-ALK | No | Yes | 3′ | No | No | NA | 1 |
| INI-1 | KIF5C-NTRK3 | Yes | No | 3′ | No | Yes | 1.17/0.19 | 1 |
1 Presence of preserved open reading frame. 2 Presence of preserved tyrosine kinase domain. 3 Presence of the chimeric transcript with the same fusion partners in ChimerDB (http://www.kobic.re.kr/chimerdb/ accessed on 21 June 2022), ChiTaRS (http://chitars.md.biu.ac.il/ accessed on 21 June 2022), and TumorFusions (https://tumorfusions.org/ accessed on 21 June 2022) databases (searched 15 June 2022). 4 Statistically significantly greater RTK RNAseq exon coverage downstream to the fusion site (t-test, p-value < 0.05 and/or the coverage of the exons downstream to the fusion site in sample with fusion was higher than 95th percentile of the same exons’ mean coverage in the control group, while the coverage of upstream exons was fitting within the 95% confidence interval (CI) of exon coverage level in samples without fusions), assessed only for the 3′RTK fusions; “ND” stands for the 5′RTK fusions. 5 Averaged expression levels of 5′- and 3′ fusion moieties calculated as RNAseq read counts normalized on lengths of exons. 6 Number of chimeric RNAseq reads. * FGFR2–LGSN transcript is absent from ChimerDB, ChiTaRS, and TumorFusions databases but was previously published in [32].