On the basis of our experience with performing AMP on 986 clinical FFPE samples, we show its potential as both a robust clinical assay and a powerful discovery tool, which we used to identify new therapeutically important gene fusions: ARHGEF2-NTRK1 and CHTOP-NTRK1 in glioblastoma, MSN-ROS1, TRIM4-BRAF, VAMP2-NRG1, TPM3-NTRK1 and RUFY2-RET in lung cancer, FGFR2-CREB5 in cholangiocarcinoma and PPL-NTRK1 in thyroid carcinoma.
More specifically, they show how alternative splicing of FGFR2 yields heteroisoforms critical to the growth-promoting actions of FGFs that exert distinct epithelial-stromal effects in thyroid cancer.
We stably overexpressed the FN target, MAGE A3, which has also been identified as a target of the breast cancer risk factor fibroblast growth factor receptor 2, and examined the functional effects in vitro and in vivo in a flank model and an orthotopic model of thyroid cancer.
FGFR-2 was the only receptor consistently detected in normal human thyroid tissue, and its expression diminished in all thyroid cancers and carcinoma cell lines, suggesting that it may have a protective role.