Real-world fusion landscape in advanced Chinese gastric cancer using next generation sequencing: A multicenter study.

Abstract

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.