Alu Methylation in Serum from Patients with Nasopharyngeal Carcinoma


Background: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia.Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome.Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels ofthis modification in serum from NPC patients.
Objective: To compare the Alu methylation levels and patternsbetween serum from NPC patients and normal controls. Materials and
Methods: Sera from 50 NPC patientsand 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) wasapplied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products wereclassified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylationat both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylatedat both loci).
Results: A comparison of normal control sera with NPC sera revealed that the latter presented asignificantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci(p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients fromnormal controls was 96%.
Conclusions: Alu elements in the circulating DNA of NPC patients are hypomethylated.Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.