Table 1.
Catalog of Fusion Partners in ROS1-Positive NSCLC
| No. | Fusion Partner | Year Published in Print/Presented |
Chromosomal Location | Fusion Breakpoint | Response to ROS1 TKI at the Time of Publication | Tumor Source | Method of Detection | Variant Frequency in Tumor (%) | FISH/IHC | References |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | CD74 | 2007 | 5q33.1 | (C6, R34) | Not treated with ROS1 TKI | FFPE | 5’ RACE RT-PCR |
NR | +/NR | Rikova et al.1 |
| 2 | SLC34A2 | 2007 | 4p15.2 | (S4, R34) | Not treated with ROS1 TKI | HCC78 cell line | 5’ RACE RT-PCR |
NR | +/NR | Rikova et al.1 |
| 3 | EZR | 2012 | 6q25.3 | (E10, R34) | Not treated with ROS1 TKI | FFPE | 5’ RACE RT-PCR |
NR | +/NR | Takeuchi et al.16 |
| 4 | LRIG3 | 2012 | 12q14.1 | (L16, R35) | Not treated with ROS1 TKI | FFPE | 5’ RACE RT-PCR |
NR | +/NR | Takeuchi et al.16 |
| 5 | SDC4 | 2012 | 20q13.12 | (S2, R32) (S4, R32) (S4, R34) |
Not treated with ROS1 TKI | FFPE | 5’ RACE RT-PCR |
NR | +/NR | Takeuchi et al.16 |
| 6 | TPM3 | 2012 | 1q21.3 | (T8, R35) | Not treated with ROS1 TKI | FFPE | 5’ RACE RT-PCR |
NR | +/NR | Takeuchi et al.16 |
| 7 | GOPC (FIG) | 2012 | 6q22.1 | NR | Not treated with ROS1 TKI | FFPE | RT-PCR | NR | +/+ | Rimkunas et al.17 |
| 2012 | 6q22.1 | (G7, R35) | Not treated with ROS1 TKI | FFPE | RT-PCR, | NR | NR/NR | Suehara et al.18 | ||
| 8 | KDREL2 | 2012 | 7p22.1 | NR | Not treated with ROS1 TKI | PPFE | DNA NGS | NR | NR/NR | Govindan et al.19 |
| 9 | CCDC6 | 2012 | 10q21.2 | (C6, R34) | Not treated with ROS1 TKI | FFPE | DNA NGS | NR | NR/NR | Seo et al.20 |
| 10 | LIMA1a | 2012 | 12q13.12 | NR | Response to crizotinib | FFPE | NR | NR | +/NR | Shaw et al.21 |
| 11 | MSNa | 2012 | Xq12 | (M9, R34) | NR | FFPE | Targeted RNA sequencing | NR | +/NR | Zheng et al. 22 |
| 2012 | Xq12 | NR | Response to crizotinib | FFPE | Targeted RNA sequencing | NR | +/NR | Shaw et al.21 | ||
| 12 | CLTC | 2014 | 17q23.1 | (C31, R35) | Not treated with ROS1 TKI | FFPE | RNA sequencing | NR | NR/NR | TCGA23 |
| 13 | TMEM106B | 2015 | 7p21.3 | (T3, R35) | Not treated with ROS1 TKI | FFPE | DNA NGS | NR | NR/NR | Ou et al.24 |
| 14 | TPD52L1 | 2016 | 6q22.31 | (T3, R33) | Not treated with ROS1 TKI | FFPE | DNA NGS | NR | NR/NR | Zhu et al.25 |
| 15 | SLC6A17 | 2017 | 1p13.3 | NR | NR | FFPE | NGS | NR | NR/NR | Zehir26www.cbioportal.org9 |
| 16 | CEP72 | 2018 | 5p15.33 | (C11, R23) | Not treated with ROS1 TKI | FFPE | DNA NGS | NR | NR/NR | Zhu et al.27 |
| 17 | ZCCHC8 | 2018 | 12q24.31 | NR | Not treated with ROS1 TKI | FFPE | NGS | NR | NR/NR | Park et al.28 |
| 2018 | 12q24.31 | (Z2, R36) | Response to crizotinib | FFPE | NGS | NR | +/NR | Hicks et al.29 | ||
| 2018 | 12q24.31 | (Z2, R36) | Response to crizotinibb | FFPE | NGS | NR | NR/NR | Zhu et al.30 | ||
| 18 | SLMAP | 2018 | 3p14.3 | (S?, R35) | Not treated with ROS1 TKI | FFPE | NGS | NR | NR/NR | Park et al.28 |
| 19 | MYO5C | 2018 | 15q21.2 | (M?, R35) | Not treated with ROS1 TKI | FFPE | NGS | NR | NR/NR | Park et al.28 |
| 20 | TFG | 2018 | 3q12.2 | NR | Not treated with ROS1 TKI | FFPE | NGS | NR | NR/NR | Park et al.28 |
| 21 | WNK1 | 2019 | 12p13.33 | (W25, R34) | PR to crizotinib | FFPE | NGS | 19.3 | NR/NR | Liu et al.31 |
| 22 | MLL3 (KMT2C) | 2019 | 7q36.1 | NR | NR | Plasma | NGS | NR | NR/NR | Dagogo-Jack et al.32 |
| 23 | CTD-2021J15.1 (LINC00973) | 2019 | 3 | NR | NR | Plasma | NGS | NR | NR/NR | Dagogo-Jack et al.32 |
| 24 | RBPMS | 2020 | 8p12 | (R1, R32) | Response to crizotinib | FFPE | NGS | 23.7 | NR/NR | Zhang et al.33 |
5’ RACE RT-PCR, 5’ rapid amplification of CDA ends reverse transcription polymerase chain reaction; CCDC6, coiled-coil domain containing 6; CD74, cluster of differentiation 74; CEP72, centrosomal protein 72; CLTC, clathrin heavy chain; DCBLD1, discoidin, CUB and LCCL domain containing 1; EZR, ezrin; FFPE, formalin-fixed paraffin embedded; FISH, fluorescence in situ hybridization; GOPC (FIG), golgi associated PDZ and coiled-coil motif containing; IHC, immunohistochemistry; KMT2C (MLL3), lysine methyltransferase 2C; LIMA1, LIM domain and actin binding 1; LINC00973 (CTD-2021J15.1), long intergenic nonprotein coding RNA 973; LRIG3, leucine rich repeats and immunoglobulin-like domains 3; MSN, moesin; MYO5C, myosin VC; NGS, next-generation sequencing; NR, not reported; TFG, trafficking from ER to golgi regulator, TMEM106B, transmembrane protein 106B; TPM3, tropomyosin 3; PR, partial response; TKI, tyrosine kinase inhibitor; WNK1, WNK lysine deficient protein kinase 1; ZCCHC8; zinc finger CCHC-type containing 8.
Both fusions were detected and treated in the crizotinib phase 2 trial. The MSN-ROS1 fusion identified in the 2 reports was likely the same identical fusion variant. One report described the technique of its identification while the other report reported its response to crizotinib in the expand crizotinib phase 1 trial.
With concurrent de novo MET amplification.