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cientists running a genome-wide analysis of pancreatic tumor samples have come across a new clue about what drives cancer metastasis. They discovered that changes in the regulation of genes — not in DNA sequences — seem to be powering the cancer’s spread.

Here’s what study author Dr. Andrew Feinberg of Johns Hopkins said about his findings, published in Nature Genetics.

What did you set out to study in epigenetics?

Genetics is the letters of the alphabet. Epigenetics is the grammar that tells genes what they’re supposed to do. It includes things like DNA methylation, which is a change in one of DNA’s four letters, the C, that silences genes. I’ve also been studying chromatin, which has to do with how compact the genes are. Sometimes they’re very compact and made inaccessible to transcription machinery, which also silences genes.

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I wanted to understand how this epigenetic info could cause cancer, because cancer cells do things that the normal cells they come from don’t do.

What did you discover about its role in metastasis?

People have simply assumed that metastases are caused by some sort of mutation. We set out to find if epigenetic changes could cause distant metastases, starting with pancreatic tumors.

We found there were large regions of the genome in the tumors that had lost the DNA methylation capability and also had lost what we call heterochromatin, the marks that make the genome squish together. They became sort of unlocked and available for genes to become active.

Genes that were within those regions were important in tumor invasion and being able to survive in a distant organ.

Do we know why that happens?

We also identified a mechanism for these epigenetic changes, involving activation of genes that protect the cancer cell from oxidative stress. When we blocked that pathway, the epigenetic changes partially reversed and the tumors lost their invasive capacity — at least in the lab. This work opens a new avenue for discovering drugs to block or reverse metastasis.

 

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