Abstract 113P
Background
Oncogenic mutations in the epidermal growth factor receptor (EGFR) serve as important predictive biomarkers in non-small cell lung cancer (NSCLC). The constitutive activity and sensitivity to EGFR tyrosine kinase inhibitors (TKIs) in lung cancer with small in-frame deletions in exon 19, mutations in exon 21 in the EGFR tyrosine kinase domain had been conferred. Atypical EGFR aberrations, including EGFR kinase domain duplications (KDD) and EGFR fusions (EGFR-RAD51, EGFR-SEPT14, KIF5B-EGFR) had been identified. Herein, we assessed the frequency of EGFR fusions in the Chinese solid tumor population to explore the possibility of therapeutic intervention in solid tumors.
Methods
A total of 9097 tumor specimen were detected using next-generation sequencing (NGS) panel to analyze EGFR fusion and other co-mutations. The statue of MSI was assessed by following the standard operating procedure (SOP).
Results
EGFR fusions were frequently associated with primary brain tumors 1.31% (13/993), biliary tract cancer 0.68% (3/443), gastric cancer 0.47% (2/428), lung cancer 0.36% (11/3051). A total of 36 EGFR fusions types were detected, of which 58.33% (21/36) retained the complete kinase domain of EGFR. We found two patterns of EGFR fusions, 58.33% with 5’-EGFR fusions (21/36, 8 gene-gene fusions, 13 gene-intergenic fusions), 41.67% with 3’-EGFR fusions (15/36, 5 gene-gene fusions, 10 intergenic-gene fusions). The breakpoints of EGFR were widely distributed but often occur in intron 7, 24, and 27. A total of 11 partner genes were detected, including the common genes SEPT14 (3/9), LOC100996654 (3/9), and novel genes LOC100996654, PKIB, PKM, CHCHD2, ABCA13, and GRB10. Interestingly, EGFR fusion concurrent with other driver mutations, such as EGFR hotspots and EGFR amplification, TP53 mutation. All patients with EGFR fusion were microsatellite stable (MSS).
Conclusions
EGFR fusions were detected in 0.32% (29/9097) of our Chinese patients. EGFR-TKIs may be effective therapeutic options in tumors harboring EGFR fusions. Combined with the diverse distribution of EGFR fusion breakpoints and the high frequency of gene-intergenic/intergenic-gene fusion, a comprehensive analysis of EGFR fusions may require the support of multiple platforms.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Mao Guibing.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.