Mutational and Expressional Analysis of DOK2 Gene in Non-small Cell Lung Cancers

Abstract

Purpose: Mounting evidence indicates that perturbation of tyrosine phosphorylation is implicated in the development of many human diseases, including cancers. Docking proteins (DOKs) are tyrosine-phosphorylated proteins that negatively regulate tyrosine kinase signaling and they are considered to be tumor suppressors. Deletion and the altered expression of the DOK2 gene have been studied in leukemias and lung cancers. However, the somatic mutation status of the DOK2 gene has not been studied in lung cancers. The aim of this study was to see whether alterations of DOK2 protein expression and somatic mutation of the DOK2 gene are present in human non-small cell lung cancer (NSCLC). Materials and Methods: We analyzed DOK2 somatic mutation in 45 NSCLCs (23 adenocarcinomas (AD) and 22 squamous cell carcinomas (SCC) by single-strand conformation polymorphism (SSCP). We examined the DOK2 protein expression in 45 NSCLCs by immunohistochemistry. Results: SSCP analysis revealed no evidence of somatic mutation in the DNA sequences encoding the DOK2 gene in the 45 NSCLCs. Among the informative cases, 27% and 21% of the ADs and SCCs showed allelic loss in the DOK2 locus, respectively. On the immunohistochemistry, DOK2 protein was expressed in the normal bronchial epithelial cells, while it was lost in 10 (22%) of the NSCLCs. Conclusion: Our data indicates that DOK2 is altered in NSCLC at the expressional level, but not at the mutational level. The data also suggests that loss of the expression of DOK2 might play roles in NSCLC development by possibly altering tyrosine kinase signaling. (J Lung Cancer 2011;10(1):26 �� 31)