Changes in DNA methylation patterns are an important characteristic of human 
cancer. Tumors have reduced levels of genomic DNA methylation and contain 
hypermethylated CpG islands, but the full extent and sequence context of DNA 
hypomethylation and hypermethylation is unknown. Here, we used methylated CpG 
island recovery assay-assisted high-resolution genomic tiling and CpG island 
arrays to analyze methylation patterns in lung squamous cell carcinomas and 
matched normal lung tissue. Normal tissues from different individuals showed 
overall very similar DNA methylation patterns. Each tumor contained several 
hundred hypermethylated CpG islands. We identified and confirmed 11 CpG islands 
that were methylated in 80-100% of the SCC tumors, and many hold promise as 
effective biomarkers for early detection of lung cancer. In addition, we find 
that extensive DNA hypomethylation in tumors occurs specifically at repetitive 
sequences, including short and long interspersed nuclear elements and LTR 
elements, segmental duplications, and subtelomeric regions, but single-copy 
sequences rarely become demethylated. The results are consistent with a specific 
defect in methylation of repetitive DNA sequences in human cancer.