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Over-expression of Repetitive, Non-protein Coding DNA Common in Tumor Cells

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Researchers at Massachusetts General Hospital (MGH) Cancer Center have discovered massive over-expression of certain non-protein coding DNA sequences in common tumor cells. The DNA sequences, called satellite repeats, have not been previously thought to have a role in cancer. The study appears in the journal Science (link below).

According to David Ting, M.D., of the MGH Cancer Center and co-lead author of the Science paper:

Satellite repeats make up a large part of our genome but had been thought to be inactive. We found that these regions are, in fact, very active in cancer but not in normal tissue. The findings may give us a novel cancer biomarker, as well as new insights into how cancers behave.

Previous studies have focused on sequences that code for proteins and excluded non-protein coding segments, which include satellite repeats, repetitive sequences of DNA often found near the centers or the tips of chromosomes. Significant expression of satellite repeats has only been seen previously in embryonic tissues or embryonic stem cells.

The current study used an advanced digital gene expression analysis system called single molecule next-generation sequencing to test DNA from epithelial cancers, the most common type of solid tumor.

Scientists first evaluated samples from a mouse model of pancreatic cancer and found that satellite DNA was expressed at levels more than 100 times what would be expected in normal tissues. Moreover, increased satellite expression was also found in mouse colon and lung tumors.

Analysis of human tumor samples produced similar results. In the majority of cancers studies, including tumors of the pancreas, lung, prostate, researchers observed high over-expression of two satellites called HSATII and ALR. The data suggests that over-expression begins early in tumor development as increased satellite expression was found in lower-grade tumors.

If confirmed in large prospective clinical trials, satellite RNA expression may provide a new and highly specific biomarker relevant to multiple types of epithelial cancers.

Study: Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers

Source: Massachusetts General Hospital