Abstract 549P
Background
Oncogenic RET rearrangement are observed in 1-2% of lung cancer. Recently, FDA has granted an accelerated approval to selpercatinib for the treatment of patients (pts) with RET alteration-positive non-small cell lung cancer and thyroid cancers. Due to the low-frequency of RET fusion in lung cancer, the fusion partners and breakpoint features of RET still need to be evaluated.
Methods
Mutation profiling was performed on 12,888 lung cancer pts (7211 males and 5677 females) from Jan. 2017 to Dec. 2019 by NGS, which covers all exons of RET and specific intron 7-11 containing the break points of fusions. The fusion patterns of RET, as well as its co-occurrence with targeted drug available mutations in lung cancer were analyzed.
Results
The pts with RET fusions, including 55 males and 79 females, were identified in approximately 1.04% of this Chinese lung cancer cohort, and the fusions mainly occurred in females (P<0.001). Totally, 145 RET fusions were detected, of which the partner genes identified by NGS were including KIF5B (91/145), CCDC6 (31/145), ERC1 (3/145), NCOA4 (2/145), TRIM33 (2/145), TRIM24 (1/145), PRKAR1A (1/145) and other unreported genes (14/145). The most frequent regions of RET fusions were intron 11 (122/148) and intron 10 (15/148) (Table). Eight RET-fusion pts (6.0%) were identified with co-mutated EGFR. Additionally, one patient (0.7%) carried an EML4-ALK fusion. Table: 549P
Frequency of RET fusions
| Partners | Pos1: Pos2 | Counts | Partners | Pos1: Pos2 | Counts | |
| Known Fusions | KIF5B91 | E15: E12 | 67 | CCDC631 | E1: E12 | 30 |
| E15: E11 | 9 | E2: E12 | 1 | |||
| E23: E12 | 4 | ERC13 | E3: E12 | 1 | ||
| E24: E11 | 3 | E5: E12 | 1 | |||
| E24: E9 | 2 | E7: E12 | 1 | |||
| E24: E10 | 2 | NCOA42 | E10: E12 | 1 | ||
| E16: E12 | 1 | E8: E12 | 1 | |||
| E17: E11 | 1 | TRIM332 | E16: E10 | 1 | ||
| E19: E12 | 1 | E10: E12 | 1 | |||
| E22: E12 | 1 | PRKAR1A | E2: E10 | 1 | ||
| TRIM24 | E9: E12 | 1 | ||||
| Unreported Fusions | DNER | E1: E12 | 1 | IL1RAPL2 | E2: E12 | 1 |
| DPP6 | E2: E12 | 1 | KIAA1598 | E2: E12 | 1 | |
| EML4 | E17: E12 | 1 | KIF13A | E18: E12 | 1 | |
| FGD5 | E1: E12 | 1 | MALRD1 | E32: E8 | 1 | |
| GADL1 | E14: E9 | 1 | SPECC1 | E4: E12 | 1 | |
| GLI3 | E2: E11 | 1 | TLN1 | E54: E12 | 1 | |
| GPRC6A | E1: E12 | 1 | ZNF33B | E4: E11 | 1 |
Conclusions
To our knowledge, this is the largest cohort to study the molecular features of RET fusions in Chinese lung cancer pts, which may result in more effective personalized diagnosis and therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.