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Analysis of Methylation in Esophageal Tumors, Nonmalignant Tissue

Cell type-specific partially methylated domains and differentially methylated domains found in normal cells persist in malignant cells, researchers from Cedars-Sinai Medical Center in Los Angeles and elsewhere report in Genome Biology. They analyzed the whole-genome bisulfite sequencing profiles of 45 esophageal tumors, representing both the squamous cell carcinoma and adenocarcinoma subtypes, and matched nonmalignant tissue. Using a sequence-aware multi-model PMD caller they developed, dubbed MMSeekR, the researchers uncovered a high level of heterogeneity at the methylation level and in the distribution of PMDs across tumor samples. Where these PMDs fall in the genome is present in normal cells, they report, but note that tumor cells exhibit a higher level of loss, and further add that cell-type-specific H3K36me2 deposition may shape how PMDs are distributed throughout the genome. Meanwhile, at the DMR level, the researchers found more than 10,000 hypo-DMRs between the two esophageal cancer types and also note that many of the methylation changes there were also present in normal cells. "To our knowledge, this is the first demonstration of the prominent cell-type specificity of PMDs across normal, precursor, and malignant states," the researchers write.