Colon, lung, and breast tumors account for 70-80% of all human tumors. Now, a team from the Bellvitge Biomedical Research Institute (IDIBELL) has investigated the genetics of these tumors, providing more data on their origin. More specifically, its epigenomic origin. The epigenome, literally ‘above’ the genome, is the set of chemical modifications that the genome undergoes. “If the genome are the letters of the alphabet – made up of 56 million nucleotides or letters -, the epigenome is the accents and spelling marks that are placed on top, ” one of the study authors, Manel Esteller, explained to Very Interesting.
Esteller and his team have obtained a drawing of the complete epigenome of one of the most common modifications (or accents), known as DNA methylation. From this drawing, which has been published in the Oncogene magazine, three fundamental photos can be extracted. One of them is the complete catalog of all the genes that have lost their protective function against tumors , because they have been “silenced” by this accent of the epigenome. A drawing has also been obtained of all the genes to which this accent – methylation – induces cell proliferation , which favors cancer. “Good genes are silenced, and bad genes are encouraged to speak,” in Esteller’s words. “All types of cancer are a mixture of both interactions in the genes”, comments Esteller.
Third, it has been seen that there are epigenetic alterations in long chromosomal regions at the same time . “It is as if we put an accent on all the words in the same sentence, without a period and followed”, which is known as hypomethylation . “We do not know why it happens,” acknowledges the researcher.
The epigenome, the first interlocutor of the environment
We are born with an epigenome that defines us as a species and as individuals, and this is modified throughout life by different factors. Some of them are age, sex … and also outside influences, such as diet, exercise, toxins … ” The epigenome is the first interlocutor of our body with the environment . Sometimes, there is an erroneous or aggressive conversation between the epigenome and the environment. After this first offensive, the genetic change finally produces , taking place the mutations that cause tumors “, Esteller has detailed for Muy Interesante.
For example, tobacco is capable of producing a genetic change , that is, a tumor inhibitor gene stops fulfilling its protective function.
Drugs that block the erroneous epigenome
Of course, the photo of tumor epigenomes implies getting closer to an effective therapy . Drugs approved for leukemia, sarcoma, and lymphoma that are capable of blocking these accents in the human genome are now available. ” The influence of the environment on the epigenome could be reversed , that is, it would be possible to eliminate the wrong interaction, erase the wrong conversation before the modifications reach the genome “, explained Esteller.
References:
E. Vidal, S. Sayols, S. Moran, A. Guillaumet-Adkins, M. P. Schroeder, R. Royo, M. Orozco, M. Gu, I. Gut, N. Lopez-Bigas, H. Heyn , M. Esteller. (2017). A DNA methylation map of human cancer at single base-pair resolution. Oncogene. Doi: 10.1038/onc.2017.176
Image: Bellvitge Biomedical Research Institute (IDIBELL).
Example of three complete epigenomes in colon cancer from a patient. The innermost concentric circle represents the normal colon tissue, the intermediate the primary colon tumor and the outermost the metastasis derived from that colon tumor. As the tumor progresses, the representation changes from dark blue to light blue, indicating the loss of the correct epigenetic signals. In the periphery with different colors we see represented the 23 human chromosomes.
