[p16/INK4a promoter hypermethylation in serum, blood and tumor of patients with esophageal squamous cell carcinoma]

ABSTRACT

Esophageal squamous cell carcinoma [ESCC] is one of the most common malignancies in Iran. ESCC patients are asymptomatic until later stages of disease which makes most interventions unsuccessful with survival rate of 5-20%. New tumor markers for early detection and/or identification of predisposing factors in ESCC may improve the life expectancy for this disease. p16, an inhibitor of cyclin D-dependent protein kinases, is a tumor-suppressor gene, with mutation and deletion reported in a variety of tumors. p16 promoter methylation is an important mechanism for inactivation of this gene and may be studied in serum DNA of cancer patients as a tumor marker. DNA isolated from serum, blood and endoscopic tissue of 30 ESCC patients and 30 normal volunteers were examined for p16 hypermethylation in province of Khorasan, North east of Iran. DNA sequences of methylated and unmethylated genomic regions after bisulfite conversion was distinguishable by sequence-specific PCR primers using methylation specific PCR [MSP]. p16 hypermethylation was found in 8/30 [26.6%] in serum samples, 13/30 [43.3%] in blood samples and 22/30 [73.3%] in tissue samples and none [0%] in normal volunteers. The 8 cases with aberrant p16 methylation in their serum DNA showed similar changes in their blood and tumor tissues. These results indicate that p16 hypermethylation may be found in the circulation with the origin of esophageal tumor DNA. Because methylation abnormalities have been found in many other genes and tumor types, this approach may have implications for noninvasive detection of a wide variety of cancers and this assay offers a potential means for the blood and serum-based detection and for monitoring of ESCC