Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors

Abstract

The receptor tyrosine kinase EPHB2 has recently been shown to be a direct transcriptional target of TCF/β-catenin. Pre-malignant lesions of the colon express high levels of EPHB2 but the expression of this kinase is reduced or lost in most colorectal carcinomas. In addition, inactivation of EPHB2 has been shown to accelerate tumorigenesis initiated by APC mutation in the colon and rectum. In this study, we investigated the molecular mechanisms responsible for the inactivation of EPHB2 in colorectal tumors. We show here the presence of mutations in repetitive sequences in exon 17 of EPHB2 in 6 of 29 adenomas with microsatellite instability (MSI), and 101 of 246 MSI carcinomas (21% and 41%, re..