Abstract 1269P
Background
Given the limited efficacy of conventional chemotherapeutic agents in non-small lung cancer (NSCLC), targeted therapies are being pursued as potential treatment alternatives. For driver gene-negative NSCLC, the detection of rare gene fusions can improve the patient's chance with medication.
Methods
We retrospectively reviewed gene test results of 437 NSCLC samples with rare fusion (excluding fusions in ALK, ROS1, RET and NTRK1/2/3) in our institute. Tumor biopsy, blood, pleural effusion or cerebrospinal fluid samples were analyzed using hybridization capture-based next generation sequencing, with white blood cells sequenced as control. This enables the assessment of single-nucleotide variants, copy number variants and structural variants (SV) in at least 59 genes (range 59-1021 genes).
Results
The cases with rare fusion included 352 adenocarcinoma, 64 squamous cell carcinoma, 6 adenosquamous carcinoma and 15 NSCLC-NOS (not otherwise specified). 76 fusions had in 74 samples medication indication and mainly focused on FGFR (60.53%), BRAF (23.68%), C15orf55 (6.58%), NRG1 (5.26%), EGFR (19.32%), RAF1 (3.95%). One sample with EGFR-FGFR1 fusion was calculated twice. Their fusion partners were summarized in the table. Among 74 patients with actionable rare fusions, 35 samples (47.30%) harbored concurrent actionable mutations and rearrangements that are recommended by NSCLC NCCN guidelines, among which 35 were EGFR positive (100%), 1 carried BRAF V600E (2.86%), MET exon 14 skipping (14.26%), 3 had ERBB2 (8.57%) mutations, 5 (14.29%) were MET amplification. The remaining 39 samples only harbored actionable rare fusions (52.70%,). For these patients, the detection of rare fusion can effectively improve the opportunity of targeted therapies. Table: 1269P
| Gene | Partner gene | N=76 |
| FGFR | TACC3, 37; EFHA2, 1; CCDC13, 1; CCDC6, 1; EGFR, 1*; KIAA1210, 1; WWOX, 1; FNTA, 1; IPMK, 1; ZMAT4, 1 | 46 |
| BRAF | TRIM24, 4; AGK, 3; EPHA1, 3; KIAA1468, 2; CUL1, 1; ERC1, 1; FAM129B, 1; MKRN1, 1; PHIP, 1; SND1, 1 | 18 |
| C15orf55 | BRD4, 5 | 5 |
| NRG1 | CD74, 4 | 4 |
| EGFR | SEPT14, 1; RAD51, 1; EGFR, 1* | 3 |
| RAF1 | ATG7, 1 | 1 |
* EGFR-FGFR1
Conclusions
Diverse rare fusions were identified in patients with NSCLC, which may explain the resistance of targeted drugs against known driver mutations and improve the opportunity for targeted therapies for NSCLC.
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.