Methylation provides clues to gastric cancer subtypes

By Helen Albert, Senior medwireNews Reporter

Research published in Science Translational Medicine shows that many gastric cancers are associated with significant epigenetic alterations along the DNA triggered by methylation.

The team, led by Patrick Tan from the National University of Singapore, carried out an analysis of the amount and distribution of methylation, which changes a gene's expression without changing the DNA sequence, occurring in 240 primary gastric tumors (n=203) and cell lines (n=37). They also analyzed 94 samples of normal gastric tissue for comparison purposes.

Tan and colleagues found that the gastric cancer "methylome" was widespread, with over half of all CG dinucleotide (CpG) sites showing signs of abnormal methylation. Many of these changes were associated with significant changes in gene expression, indicating that the epigenetic alteration caused by the observed methylation is likely to be functionally significant.

A subtype of gastric cancer known as the CpG Island Methylator Phenotype (CIMP) has previously been proposed and its existence, characterised by very high levels of methylation, was confirmed in this study.

The CIMP subgroup was primarily seen in younger patients with a poor prognosis and initial laboratory tests suggest that these tumors may be sensitive to demethylating drugs.

"Our study does provide clarity in unambiguously demonstrating the presence of this subgroup and its features," commented Tan in a press statement.

"What's more, we are encouraged that there may be potential utility in testing the sensitivity of CIMP tumors to more potent DNA demethylating agents and possibly other epigenetic drugs."

Other distinctive features of the gastric cancer methylome included long-range regions of epigenetic silencing targeting regions or individual genes.

"Our results strongly demonstrate that gastric cancer is not one disease but a conglomerate of multiple diseases, each with a different underlying biology and hallmark features," Tan remarked.

"If gastric cancer is the result of multiple interacting factors, including both environmental factors and host genetic factors, we need better ways to diagnose and treat it," he emphasized.

"These findings move us forward, and additional work will focus on developing simple diagnostic tests to detect gastric cancer at earlier stages, plus drugs and drug targets that might exhibit high potency against different molecular subtypes of disease."

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