Culture may be an important factor to consider when analyzing men's help-seeking behaviors in response to a prostate cancer diagnosis. In order to explore what role culture might play when men make decisions regarding their prostate cancer, a systematic review of the literature spanning nine research databases took place. Those research databases were: PsychINFO, PubMed, Medscape, Web of Science, Google Scholar, BIOSIS Previews, JSTOR, PsychArticles and ScienceDirect. While many researchers state culture may play a role in defining a man's help-seeking behaviors after prostate cancer has been diagnosed, the literature fails to show, with convincing evidence, information that is necessary to understand this finding. Understanding how men make decisions about their health needs has to be expanded beyond men and women. Therefore, more research must be done that analyzes men's help-seeking behaviors with cancer from a cultural perspective. The lack of information in the literature leaves a potentially integral factor in men's help-seeking behavior out of the realm of consideration, and more research on the subject would be beneficial to the field. 

Clonal evolution is a key feature of cancer progression and relapse. As cancers progress they accumulate large numbers of mutations. Some of these mutations are present in all of cells (clonal mutations) and drive the malignant progress. We will ask if there are other mutations that are present in only a subset of cells within tumors; as the environment changes during therapy these could become new driver mutations and could be the source of resistance to therapy. The subclones with the best evolutionary fitness will, in time, come to dominate the cancer cell population. Studying the number and identity of subclonal mutations may help us to predict whether or not a tumor has potential resistance to different drugs. Our hypothesis is that the large amount of subclonal mutations within a cancer will increase the overall fitness of the tumor, by providing a greater diversity from which new phenotypes can arise. We will modify the newly developed sequencing methodology, termed Duplex Sequencing, to identify specific subclonal mutations present in colorectal cancers. By adding a barcoded, partially non-complementary adapters to both ends of an individual DNA molecules which allow mutations in both strands of a DNA duplex to be identified, this approach greatly reduces sequencing errors. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors result in mutations in only one strand and can thus be identified as technical error. We believe that most colorectal cancers will have a complex subclonal structure and may show clusters of subclonal variants, including subclonal driver mutations. Furthermore, presence of a subclonal driver mutation may be an independent risk factor for disease progression. Our study will thus uncover patterns of mutational evolution in colorectal cancer, providing insights into its stepwise clonal evolution.

Polymerases epsilon and delta are responsible for replicating the leading and lagging strands of DNA, respectively. Accurate DNA replication occurs through Watson-Crick base pairing catalyzed by the enzymes’ polymerase domains, and also through the action of the polymerases’ exonuclease (proofreading) domains. The exonuclease domain of polymerase epsilon (POLE) has recently been reported to be mutated in ~4% of sporadic colorectal cancers and is associated with a high frequency of clonal base substitutions throughout the tumor genome. We hypothesize that the extent of mutational heterogeneity within a tumor will be predictive of the likelihood of resistance to any given chemotherapeutic agent and that the mutational heterogeneity due to mutations in POLE may also allow us to clinically stratify patents.The ultimate goal of the project is to identify POLE mutations in a tumor tissue, if applicable, and to find the quantity of mutations to compare with normal tissue and tumor tissue without POLE. I will utilize the newly developed Duplex Sequencing methodology to identify mutations that are present in a small number of cells within a tumor. By independently tagging and sequencing each of the two strands of individual DNA duplexes, this approach greatly reduces the number of errors. As the two strands of DNA are complementary, true mutations should be found at the same position in both strands. I will first identify tumors carrying somatic POLE mutations and use Duplex Sequencing to quantify the subclonal mutational load. My research team and I expect that the extent of mutational heterogeneity will be greatly increased in tumors bearing POLE mutations due to its impairment of proofreading capacity. For the symposium, we hope to present the quantity of sequencing errors in each of the tissues listed above or at least explain the process if we fail to collect the results in time.