P53 in breast cancer and its role in chemotherapy efficacy

The TP53 gene is one of the most common genes seen in breast cancer tumor cells which codes for the P53 protein. For years scientists have known about the frequency of P53 seen in breast cancer cells, but only recently have they begun to explore the role of mutations in this protein and how they affect the overall effectiveness of chemotherapy.

The first paper I read was written in 1998 and it studied 40 tumors; 29 of which were linked to BRCA1 and 11 of which were linked to BRCA2. The scientists examined the tumors for mutations in various genes linked to breast cancer development, one of which being the TP53 gene. One of the most staggering statistics gathered from this study was the fact that P53 mutations were seen in 80% of the tumors, affecting 83% of BRCA1-linked tumors and 73% of BRCA2-linked tumors. Mutations of P53 most commonly resulted in the upregulation of the protein which was most likely the result of a change in the cell cycle checkpoints. The paper concluded that even though P53 may not be mutated in every case, different components of the P53-dependent cell cycle could have been altered which may have a direct effect on the tumors.

The second paper I read was written by French scientists in 2013, and the study was prompted because the scientists realized that even though previous findings showed an obvious central role of P53 in cancer, the status of TP53 has never been studied as a way to manage breast cancer. Mutations of the TP53 gene are the most common across all breast cancer sub-types, seen in 30% of tumors. In breast cancer patients, tumors are determined to be ER(+) or ER(-), meaning they are either receptive (+) or nonreceptive (-) to estrogen. The paper suggested that having a tumor that is ER(-) with TP53 mutations is the best case scenario for patients, because the accumulation of genetic mutations and abnormalities in these tumors lead to a better response to chemotherapy compared to ER(+) TP53 wild type tumors.

After reading these two articles, it is clear that there is much more research needed in this field for any hope of finding a way to completely eliminate these tumors. The largest challenge when treating breast cancers is the fact that there are so many types of tumors which can range in their response to chemotherapy. I believe these studies are huge leaps forward for the field of oncology, but more studies need to be conducted on P53 as well as any other genes thought to play a role in any stage of tumorigenesis. I think for now studies should focus on P53 due to its widespread activity in breast cancer because it may hold the secrets to the main pathways that allow for tumor growth. If we can find even one pathway responsible for tumor growth, we may be able to break the pathway and cure cancers that were difficult to near impossible to treat before.

Links to articles:

Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers:
https://cancerres.aacrjournals.org/content/canres/58/15/3193.full.pdf

p53 in breast cancer subtypes and new insights into response to chemotherapy:
https://reader.elsevier.com/reader/sd/pii/S0960977613001409?token=928B8AEBFB15502B20406BA94D56BD2D5DFDEB8F1AE42F99BBCC1C8D495CC458BC5BB9A7324D713715B1B69FE7332585

Genes that have Effect on Head and Brain Size

            It was recently discovered that the size of children heads is not only related to the size of their skull, but also to the size of their brain. This discovery was published in Nature Communications, on how a genome-wide analysis can identify the genetic effects of head size and if it is related to the size of the brain. Up until the age of six, children and baby heads are measured throughout their life to make sure they are having healthy growth developments with their brain as they age. However, scientists at the Max Planck Institute (MPI) researched a genome-wide study (GWAS) with 46,000 adult and children to collect data on the effects of head size and brain size. The team suggests from the data collected, that an adult’s final head size is genetically predicted at a young age. The team also discovered that a rare gene, that about only two percent of the population contains, is called TP53. TP53 is a gene that encodes for p53, which controls cell division. TP53 is known to have mutations, but p53 is known as a gene to thicken the membrane of the skull bone, which can result in a larger brain size. 

       Although this article is very interesting that scientists are researching genes that can determine how large a person’s brain can become just by measuring the size of a person’s head when they are a baby. I do not think that the scientists have enough information to be able to say they can measure a baby’s head and determine if that baby will grow up and be the smartest child in school or an average child in school. The scientists only discovered that the TP53 gene can encode to the p53 protein which may be a factor to the thickness of a person’s skull, but this gene is only found in about two percent of the population. There would need to be more studies on the TP53 gene to determine if it actually is the factor for a larger head size, which can then determine if a larger head size results in a larger brain.

LIF6 Gene Could Be Causing Low Rates of Cancer in Elephants

        Hundreds of thousands of Americans die yearly due to cancers. A disease that appears in such large numbers in the human species is rare to be found in the elephant species. The article Elephants Revived a "Zombie" Gene that May Fend Off Cancer talks about how these low rates of cancer found in elephants may be due to a "zombie gene". It is a defunct duplicate of the LIF gene that was brought about in evolution. When there is damage to any DNA in an elephant, the elephants' cells will increase the activity of the zombie gene, LIF6, destroying the cell completely. Researches declare that this destroys any genetic defects that are caused by cancer. The LIF gene has numerous functions in mammals. In elephants, the LIF gene is duplicated several times as pseudogenes. These genes do not have the correct sequence to produce functioning transcripts. Researchers question whether these duplications may have an affect on the elephants' cell response to any DNA damage, which is completely destroying it. 

        The team of researches found that the LIF6 gene, one of the duplicated pseudogenes, had duplicated in a way that it produces a transcript. That specific gene product is controlled by TP53 which is a tumor suppressor.  The TP53 protein regulates cell division and keeps the cell from dividing and growing at too quick of a rate or in an uncontrolled way. The over expression of LIF6 in the cells of elephants cause the cells to undergo apoptosis, causing the death of the cell. Researchers then had the idea to introduce the gene into the ovary of a Chinese hamster. When they did, the results showed that the gene had the same response to any DNA damage, complete destruction. There is still more work to be done to confirm the relationship between the LIF6 gene and low rates of cancer. This is definitely an interesting genetic discovery and could lead to many interesting findings in future research. I believe this discovery will lead to medical advancements in cancer treatment in the future. Since cancer rates and deaths due to cancer are so high in the United States, research like this gives hope that a cure can still be found.

Can Cigarettes Increase the Likelihood of Twins?

Researchers at the University of South Florida have discovered a link between cigarette smoking and the increased chance of an African American mother receiving twins. The study consisted of 2200 African American woman who have gone through labor, including 227 who have given birth to twins.      The study showed that a specific SNP (single nucleotide polymorphism) in the TP53 gene combined with smoking habits showed an increased likelihood of twins. These results were contrary to popular belief of how smoking may cause infertility and miscarriage. Instead, the presence of both the TP53 SNP and cigarette smoking promoted the chance of receiving twins in African American parents.

The results showed that there is a genetic link between the chance of having multiple births and ones DNA. However, due to the small sample size in the experiment, the results might not be entirely conclusive. Instead I believe this experiment might promote smoking in some mothers, which should not be the case. A mother that might want to increase the chance of receiving twins might view this article and decide that cigarette smoking will help to achieve this. This will be harmful to the newborn baby and should not be promoted whatsoever.