Aggressive Skin Cancer and DNA

When it comes to screening for or treating cancer at the DNA level, knowing the DNA sequence in a patient is sometimes just part of the picture. Certainly this would appear to be the case with more aggressive cancers such as Melanoma. In these types of cancer, yes, there may (or may not) be a predisposition within the DNA, but other forces come into play that may be entirely divorced from anything in the initial code.

 

The gene sequence informs the cell's engine room about what building blocks should be in place, but the engineers do not always follow the plan and materials may be placed in the wrong positions. These errors are know as epigenomic changes and it has been found that these changes play an important role during the progression of melanoma.

Melanoma is a type of skin cancer, which is quick to metastasize and does not respond well tor treatments. The study, published in Nature Communications, reports, "a significant step forward in the characterization and potential treatment of melanoma." Profs Stein Aerts (KU Leuven) and Chris Marine (VIB/KU Leuven) were able to confirm that epigenomic changes play an important role in the development and progression of melanoma.

So, these cancers do not arise from mutations or errors in the DNA itself but are the result of changes in the stream of information from the DNA to the cell. In a first phase of cancer, specific proteins bind themselves to specific locations in the DNA, which allow the tumour to grow. In a second, more aggressive phase, other proteins are activated that bind to other DNA sites, which allow the cancer cells to invade and spread to other tissues in the body.

Professor Aerts and his team succeeded in mapping the epigenomic landscape in both phases of melanoma progression. They identified the proteins and the thousands of regions on the DNA to which the proteins bound themselves. Furthermore, when the researchers knocked out these proteins, the melanoma became much less aggressive and more receptive to existing cancer drugs.

This is the first complete epigenomic profile of melanoma and the first study to map the regulatory landscape of the different melanoma cell states. The results contribute to a more complete picture of cancer cells during melanoma progression and constitute an important step forward in the search for more targeted, more effective therapies for this aggressive type of cancer.