There are currently no reliable serum biomarkers for the diagnosis or treatment of patients with lung cancer. Several tumor suppressor genes, including APC, p16, MGMT, DAPK, and GSTP1, are known to be hypermethylated in lung tumors, and these methylated genes can be detected in the blood of lung cancer patients. When DNA is treated with bisulfite, differences in the DNA sequence develop between methylated and unmethylated genes. Methylation-specific PCR (MSP) can then be used to selectively amplify hypermethylated genes specific to tumors, and distinguish their presence amidst normal DNA. We have developed a technique which combines TaqMan(r) real-time PCR with MSP. This technique, called TaqMan(r)-MSP, provides higher sensitivity and specificity than conventional MSP for identifying methylated genes in the blood of cancer patients. Furthermore, TaqMan(r)-MSP is a high-throughput test, allowing for the rapid analysis of multiple genes in multiple samples, with quantitative as well as qualitative measurements generated for comparison. In this study, we propose to evaluate the effectiveness and utility of TaqMan(r)-MSP to measure the quantity of hypermethylated genes in the blood of patients with early stage, and advanced lung cancer. We will take the novel approach of measuring the quantity of multiple different hypermethylated genes in blood at timepoints before, and after therapy (surgery, or chemotherapy). The goal of this study is to explore the ability of TaqMan(r)-MSP to detect the presence of hypermethylated genes in the blood of lung cancer patients. Future studies will be required to establish this technique as a reliable diagnostic tool to guide the management of patients with lung cancer.
| Li, B T; Drilon, A; Johnson, M L et al. (2016) A prospective study of total plasma cell-free DNA as a predictive biomarker for response to systemic therapy in patients with advanced non-small-cell lung cancers. Ann Oncol 27:154-9 |
| Drilon, Alexander; Sugita, Hirofumi; Sima, Camelia S et al. (2014) A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage I to IIIA non-small-cell lung cancers. J Thorac Oncol 9:1272-7 |
