Cancer is caused by mutations that either turn on the expression of oncogenes or turn off the expression of tumor suppressors. Oncogenes are elements that promote growth and cell division while tumor suppressors slow down the cell cycle and work to keep the cell from dividing. In a normal cell, there is an interplay between the two to ensure that cells only divide when it is necessary. In cancer cells, cell growth is rampant and out of control. How does a cell turn on an oncogene or turn off a tumor suppressor? In the past, we’ve always assumed that there was DNA damage. A mutation could happen in a gene that either keeps it from being expressed or alters its subsequent protein to make it be constitutively active. Are there other ways in which cancer can arise?
I sat in an interesting lecture yesterday regarding the epigenetics of cancer. Epigenetics defines changes in gene expression that cannot be explained by DNA damage or alteration. DNA is bundled in the cell nucleus by winding around histones to make it more compact. These histones have tails that can be modified in order to make the DNA more open and available for gene transcription or more compact and silenced. The genetic code is comprised of four bases, of which cytosine can be methylated leading to DNA silencing. Changes in gene expression can occur epigenetically to cause expression of oncogenes where they should not be or silencing of tumor suppressors where they are desperately needed.
Epigenetic changes in cancer are a current “hot topic” in research, and there is a lot that needs to be studied. When it comes to DNA mutation, there are many checks and balances to keep changes from being passed on to the next generation of cells. Occasionally, a mutation makes it past the DNA repair mechanisms, and this can lead to pre-cancerous changes. However, there are no checks and balances with epigenetics. The expression levels of genes must be more fluid and ever-changing in order to give rise to so many different tissues and organs in the human body. The DNA sequence is the same between the heart and the brain. However, there are vastly different epigenetic gene expression profiles between the two organs. During development and even during the lifetime of a cell, gene expression needs to be able to subtly shift depending on the environment and destiny of the cell. Therefore, it is easy to see how mutations in the epigenome can occur much more easily than mutations in the nuclear genome.
What is to be the next focus of scientists studying the epigenetics of cancer? Currently, scientists are scanning the epigenome of many thousands of tumors in order to get a good picture of which tumors have which changes. Just as it is with DNA mutations in which some genes are mutated much more in one cancer over another, such as the BRCA1 mutation in breast cancer, scientists are finding similar results in the epigenome. Finding such pattern in the epigenome will give scientists a jumping off point for further research into cancer treatments.