Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients

Recent evidence suggests that tumor cells may release DNA into the circulat ion, which is enriched in the serum and plasma, allowing detection of ras a nd p53 mutations and microsatellite alterations in the serum DNA of cancer patients. We examined whether aberrant DNA methylation might also be found in the serum of patients with non-small cell lung cancer. We tested 22 pati ents with non-small cell lung cancer using methylation-specific PCR, search ing for promoter hypermethylation of the tumor suppressor gene p16, the put ative metastasis suppressor gene death-associated protein kinase, the detox ification gene glutathione S-transferase PI, and the DNA repair gene O-6-me thylguanine-DNA-methyltransferase, Aberrant methylation of at least one of these genes was detected in 15 of 22 (68%) NSCLC tumors but not in any pair ed normal lung tissue. In these primary tumors with methylation, 11 of 15 ( 73%) samples also had abnormal methylated DNA in the matched serum samples, Moreover, none of the sera from patients with tumors not demonstrating met hylation was positive. Abnormal promoter methylation in serum DNA was found in all tumor stages. Although these results need to be confirmed in larger studies and in other tumor types, detection of aberrant promoter hypermeth ylation of cancer-related genes in serum may be useful for cancer diagnosis or the detection of recurrence.