Turn off the switch for thyroid papillary carcinoma cancer!!!

Primary article:
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.

News article:
Szabo, L. (2004, Nov.9). Taking on thyroid cancer. USA Today 11D

The scientific article (Cohen et al., 2003) has been cited in other primary scientific articles. The most recent three are the following;
Kambara, T., Simms, L., Whitehall, V., Spring, K., Wynter, C., Walsh, M., et al. (2004). Colorectal cancer: BRAF mutation is associtated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53, 1137-1144

He, H., Jazdzewski, K., Li, W., Liyanarachchi, S., Nagy, R., Volinia, S. (2005). The role of microRNA genes in papillary thyroid carcinoma. PNAS 102, 19075-19080

Xing, M. (2005). BRAF mutation in thyroid cancer. Endocr.Relat.Cancer 12, 245-262

The type of cancer that the articles address is papillary thyroid carcinoma, the most common form of thyroid cancer; and anaplastic thyroid cancer which; is most often fast growing and fatal. The other cancers mentioned are melanoma; lung, head and neck cancers; as well as other less common thyroid cancers.

Carcinoma- “An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body”. http://dictionary.reference.com/browse/carcinoma%
Melanoma- A dark-pigmented benign or malignant tumor that arises from a melanocyte and occurs most commonly in the skin. Malignant melanoma metastasizes quickly and is associated with sun exposure. http://dictionary.reference.com/browse/melanoma
Summary:
The new research that is described in the primary study is that the BRAF mutation is involved in papillary thyroid cancer. The study was done at Johns Hopkins University School of Medicine. The researchers already knew that BRAF was linked to melanoma, and that there must have been a genetic mutation in papillary thyroid cancers. Thus they tested for it in thyroid cancer as well as the other cancers mention above.
The researchers did a test on 476 tumors, for 214 lungs, 126 head and neck, 54 thyroids, 27 bladder, 38 cervical, and 17 prostate cancers for BRAF T1796A mutation by polymerase chain reaction. These samples were taken from the patients and were kept in the tissue bank.

Through their experiments, Cohen et al found a mutation in the BRAF T1796A gene in 69% of papillary thyroid cancers. They discovered that there was a misinterpretation in the chemical bases in the following amino acid (adenine, thymine, cytosine, and guanine that help build up DNA. In the BRAF gene in the nucleotide 1796 it changed (T) thymine to (A) adenine. The researchers discovered that a single coding mistake in more than 2000 in the nucleotides in gene made it stay on the “on” position, causing thyroid cells to proliferate and divide into a cancer. They screened for the BRAF gene mutation in different types of cancers and thyroid tumors. They did not find any mutation in the biopsy samples of the 20 sample of benign thyroid, 13 of the patients had follicular, and 3 with medullary thyroid carcinoma and Hurthle cell carcinoma. This was not found in some other thyroid cancers, nor in cervical, prostate, or bladder cancers.

The primary scientific article describes in great detail the BRAF mutation, its role in malignant melanoma, and how it could relate to papillary thyroid cancer. The researchers explained their methods, using scientific terms for cell lines, mutations, and genes. On the other hand, the USA Today article talks about other thyroid cancers, and mentions there are many new studies all over the country, not just at Johns Hopkins. However, the articles give in the same information about one finding, but in very different languages. The primary article states that “The high frequency of BRAF mutations in melanoma and papillary thyroid carcinoma suggests that inhibition of BRAF activity by the newly developed RAF kinase inhibitors (12) may offer a new strategy in the treatment of these tumors.” On the other hand, the secondary article states “the gene, called BRAF, acts as an on/off switch for cell growth. In tumors with the mutation, this switch gets stuck in the “on” position.” Most readers without a scientific background can understand about an on/off switch, but not about RAF kinase inhibitors.

My reaction to the information provided in the primary article is that it is very helpful for people who are interested in doing research. There were a few charts and tables that helped me to understand the results of the research, and what was the researchers purpose. The secondary article was extremely simple to understand the audience does not have to be scientists or a science majors to understand; what was being done. I trust the primary article more because it has more reliable information and it is written in a way that you know a scientist or a researchers who knew what they were doing or talking about wrote the article. However, the secondary article does quote scientists from notable research centers, including David Sidransky, who was one of the researchers in the primary article (et al.!) and is the director of the Johns Hopkins University School of Medicine.

Question
why does chemo and radiation therapy only shrink the anaplsatic tumor for a short period of time?
Why is the activation of BRA mutations is so important in development of papillary thyroid cancer?