A bigger sandbox

Studies reported in the online version of Science magazine last week represent a breakthrough in researchers’ understanding of melanoma. Reading about them in Science didn’t mean much to me ... so I embarked on a mission to learn. Perhaps I can write about this in a way that will help others understand, too.

First, I needed to understand more about DNA. Everyone has heard of it, and we know some of the language – genes carry the code, and chromosomes carry the genes. Younger folks probably learned more, but that was the extent of my understanding. When these reports started talking about the “dark matter,” they left me behind. Robert’s oncologist, Evan Lipson of Johns Hopkins University Hospital, helped me get started.

There are two kinds of DNA, he explained, not just the one we all know about – the genetic instructions that tell a cell what to do. This kind he likened to a manual for a stereo or for putting furniture together: “put part A into slot B.”

The actual instructions make up a very small portion of the DNA, about 1%. The other 99% is what they call dark matter – and this Dr. Lipson likened to “the instructions for the instructions.” For example, he said, “make sure you have a screwdriver and a wrench.” Although these instructions make up the bulk of the DNA, for the most part they have been dismissed in the past as “junk,” according to an article in the Harvard Gazette. All cancer-causing mutations found in the past have been in the instructions, not the dark matter.

The new studies found mutations in the “TERT promoter” area of DNA in 50 of the 70 melanomas examined. The TERT gene carries instructions for producing an enzyme, telomerase, that can make cells virtually immortal and has been found “overexpressed” in cancer cells, according to the Harvard publication. The “promoter” region is located near the gene and acts as a control point to tell the gene whether to perform its function. It’s possible that  mutations in the TERT promoter area cause the gene to over-produce the enzyme – hence the description “overexpressed.”

Other genetic mutations have been associated with melanoma. The most prevalent one is of the BRAF gene, and a lot of the therapeutic research to date has benefited the estimated 48% of metastatic melanoma patients who have tested positive for this mutation. With the TERT-promoter mutation affecting about 70% of melanoma tumors examined in the recent study, the potential is there for this finding to lead to therapies that would help even more patients with melanoma.

It’s important to note that such treatments are a long way off. But Dr. Lipson agreed with my description of what this finding means for cancer researchers – that their sandbox just got bigger. “What they have showed now is that the components of that dark matter, which until now were not very well defined, may have bearing on the way melanoma progresses and the way cells are or are not controlled by the body. It becomes another potential target, another potential site of investigation for therapeutic intervention,” he said.

We’ll take every advance we can get.

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