Label-free electrochemical detection of human methyltransferase from tumors

Abstract

Abnormal DNA methyltransferase activity has been implicated in cancerous transformations and tumorigenesis; efficient detection of methyltransferase activity could provide an early cancer diagnostic. Currently, most detection platforms involve fluorescence or radioactivity, making them cumbersome. Electrochem. platforms, in contrast, offer high portability, sensitivity, and ease of use. We have developed an electrochem. DNA array platform that is formed and addressed using a secondary electrode, allowing for both formation of dil. DNA monolayers and optimized detection through DNA-mediated charge transport with electrocatalysis. This label-free electrochem. platform has been used to successfully detect the activity of the most abundant human methyltransferase, DNMT1, in crude lysates from both cultured human colorectal cancer cells (HCT116) and colorectal tissue samples. We addnl. distinguish colorectal carcinoma tissue from healthy adjacent tissue through differences in DNMT1 activity, demonstrating the utility of this two-electrode platform for clin. applications.