Abstract
The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.
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Acknowledgements
This study was partly funded by grants from the Spanish Fondo de Investigaciones Sanitarias (FIS PI051394) and from the FMM to DA; Deutsche Krebshilfe Grant (Kn) to JG and SW; Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to HY and KI, POCTI/SAU-OBS/56921/2004 da Fundação para a Ciência e a Tecnologia of Portugal to RS, NIH, Grant number R37 CA63585 to MP; and ICIC, Fondo de Investigaciones Sanitarias (FIS-ISCiii-RTICCC), Fundación Canaria de Investigación y Salud (FUNCIS) and Dirección General de Universidades del Gobierno de Canarias to N D-C and JC D-C, grant from Fundação para a Ciência e a Tecnologia, Portugal to AMF and Grants-in-Aid for Cancer Research and for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan to HY and KI. VD is supported by a predoctoral fellowship from the Vall d'Hebron Research Institute.
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Davalos, V., Dopeso, H., Velho, S. et al. High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability. Oncogene 26, 308–311 (2007). https://doi.org/10.1038/sj.onc.1209780
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DOI: https://doi.org/10.1038/sj.onc.1209780
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