ABSTRACT
MGMT, and DARK Genes .............................................................................. 722 41.4 Results .......................................................................................................................................... 722
41.4.1 Device Characterization and Surface Modication ........................................................ 722 41.4.2 Direct Electronic Detection of DNA Methylation .......................................................... 724 41.4.3 Indirect Electronic Detection of DNA Methylation ........................................................ 725
41.4.3.1 Enzymatic Cleavage of Signal Probe ............................................................... 725 41.4.3.2 Electronic Detection of Signal Molecules ....................................................... 725
41.4.4 Detection Sensitivity ....................................................................................................... 726 41.5 Discussion .................................................................................................................................... 726
41.5.1 Label-Free and Ultrasensitive ......................................................................................... 727 41.5.2 Improved Detection Specicity ....................................................................................... 727 41.5.3 Simple Procedure without Bisulfate Treatment .............................................................. 728 41.5.4 Universal and Low-Cost Devices .................................................................................... 728
41.5.4.1 Nano-FET Surface ........................................................................................... 728 41.5.4.2 pH and Salt Concentration in the Samples ...................................................... 728
41.6 Future Trends ............................................................................................................................... 728 41.6.1 Where the Technology Is Going ...................................................................................... 728 41.6.2 Future Applications ......................................................................................................... 729
Acknowledgments .................................................................................................................................. 729 References .............................................................................................................................................. 729
Early cancer diagnostics is one of the most important issues in health care. Early diagnostics directly in•uences the choice and effectiveness of therapy treatment which impacts cancer patient survival. To improve diagnostics in the earlier stage of tumor development, research is focused on two important factors: (a) discovery of new cancer biomarkers which report early events in tumor initiation, and (b) development of new molecular detection technologies which utilize small samples and are ultrasensitive and low cost. Current cancer diagnosis depends on a variety of factors including illness symptoms, imaging, blood test for protein markers, and biopsy pathological microscopic analysis. The limited sensitivity associated with these methods can result in the delay of diagnosis and treatment. Numerous new biomarkers for cancer are being discovered [1-3]. Among these new discoveries, epigenetic alteration such as methylated cytosine in the regions of high CpG content in gene promoters is one of the earlier events that occur in tumor development [4-7]. These high CpG content regions, referred to as CpG islands, are considered an important factor that in•uences cell growth, differentiation, proliferation, and apoptosis through mechanisms of transcription or posttranscriptional regulation of gene expression [8]. Abnormal DNA methylation at specic gene transcription sites can result in epigenetic silencing of tumor suppressor genes that prevent tumor formation or play a critical role in DNA repair [9,10]. Both are important factors of tumor initiation. In normal cells, most promoter-associated CpG islands are unmethylated, but in cancer cells, methylated CpG islands are often observed. A high level of hypermethylation in the promoter region of tumor suppressor genes was identied within sets of tumors. Thus, detection of DNA methylation in the promoter region of tumor suppressor genes can be an important assay in early cancer diagnosis. In addition, detection of DNA methylation in diagnosed cancer patients may provide important information about the subtype of cancer and the effectiveness of potential treatments. This information will allow oncologists the ability to better understand each individual case and develop strategies for personal treatment.
