What can a mutation in the BRAF protein do to me????

Possible Cure for Skin Cancer????? Blog by Charlene C.
Futreal, Andy. June 10. 2002. “ British Scientist Identify Skin Cancer Gene”. The New York Times. June11.2002. http://ww.nytimes.com/

Turn off the switch for thyroid papillary carcinoma cancer!!! Blog by Tanya M.
Cohen,Y., Xing, M., Mambo, E., Guo., Z., Wu. G., Trink, B., et al. (2003 April) BRAF mutation in papillary thyroid carcinoma. Journal of the National Cancer Institute, vol. 95, No.8.

I believe that developing a possible cure for skin cancer is vital because this disease is very common; everybody who is exposed to UV light is at risk of getting skin cancer. Although skin cancer may be dormant for years, one has to remember that cancer is a work in progress, which means it takes time for symptoms to occur. Finding a drug that could inhibit the mutant BRAF in cancer cells would save lives; that way, we can at least stop the tumor cells from proliferating. When BRAF proto-oncoprotein is constantly activated that leads to uncontrollable growth. BRAF protein is similar to RAF which is in the RAS-MAPK pathway. BRAF is activated when an adaptor protein helped Ras become activated by binding GTP to it instead of GDP, then activated Ras would then bind BRAF, which would become phosphorylated, and it would become active. BRAF is a kinase (an enzyme that catalyzes protein phosphorylation), and when it is active, it phosphorylates other proteins, like MEK and MAPK and then pass on the pro-growth signal to the nucleus. This article is extremely important because not only did the results of the experiment pave the way for future research about skin cancer, they also discovered a way to create an inhibitor that slowed down the kinase for a similar protein to BRAF called the ABL protein. ABL protein acts as a proto-oncoprotein in most normal cells. However, the finding states that ABL was present in patients diagnosed with leukemia. It is unknown to me whether what the researchers found in the patient diagnosed with leukemia was a mass of ABL protein or a mutated ABL protein.
While reading these fascinating blogs, I discovered a common molecular event between these two articles: Possible Cure for Skin Cancer????? and Turn off the switch for thyroid papillary carcinoma cancer!!! discussed by Charlene C. and Tanya M. I found these two articles interesting because they both examine the relationship between BRAF in cancer; in fact the research in Charlene C’s article was the basis for the scientists to see if the mutated gene BRAF was present in papillary thyroid cancer. Both papers explored the BRAF gene which is found in normal cell types as well as cancerous cell types. What is fascinating is that Cohen et al knew that BRAF mutation was involved in thyroid cancer and that BRAF has a connection with melanoma through the experiment that they did in June2002. Therefore, with this knowledge they were able to make new hypothesis and did further experiment. The result of their new experiment showed that there was a mutation in the BRAF gene (T1796A) in 69% of papillary thyroid cancers. They discovered that nucleotide 1796 in BRAF was changed from thymine (T) to adenine (A), and this single change was enough to contribute to BRAF always being “on” which then causes the thyroid cells to proliferate and then eventually become cancer cells. Both these findings may pave the way for chemotherapy to deactivate the mutated BRAF protein. While reading these articles, I noticed a lot of similarity to what we have learned in class especially knowing that when something that should not always be turned on is on. We know that then chaos will happen; there will be uncontrollable growth which in turn becomes malignant tumor. The similar research Cohen et al did was that even though they knew that a mutation in BRAF can be labeled as an oncogene in cancer patients, they could not identify the specific point mutation in the most malignant melanomas. The scientists then created a study in which they can separate the normal cells from the tumor cells and did an experiment to figure out in which cell types BRAF is most active and found that BRAF was present in the patient’s DNA who had cancer. They screened the BRAF gene mutation in different type of cancers. There were no differences in the results described about the on and off switch.
I have several questions I would like to pose regarding this information: besides the spontaneous changes that can happen within the cells when proliferating and mutation, what is the main thing that can distract a gene which stops it from doing what it’s supposed to do? For example, why would the BRAF gene in T1796A change T to A? How do these genes get activated? In addition, I am curious about environmental triggers: can the environment cause the mutations to be turned on? Or can an individual’s life style such as obesity set off the gene?