TMC PULSE

t m c » p u l s e | s e p t e m b e r 2 0 1 5 18 18 By contrasting an individual's cancer cells with one of his or her normal cells, the changes that resulted in the malignancy become apparent. The simplicity of it is as elegant as the biology itself, but, as with most science, it also has the potential to be misleading—especially when you move towards developing therapeutics to confront the mutations. Designing cancer treatments based on genomic evaluations is exceedingly difficult for many reasons, perhaps most of all the inherent heterogeneity of the disease, which in the simplest terms describes the complexity of the composition of cancerous tissue. "There is a lot of intricacy in cancer cells and the process of malignancy," explained Andrew Futreal, Ph.D., Chair Ad Interim in the department of genomic medicine at The University of Texas MD Anderson Cancer Center. Notably, MD Anderson was recently named one of two new Genome Characterization Centers funded through the National Cancer Institute. "The biggest challenge in finding clinically useful information via genomic data is comprehending heterogeneity. Not only are tumors heterogeneous from one patient to another, but there is also intra-tumor heterogeneity, wherein the same tumor accumulates different kinds of mutations over time." Futreal, who is known in the world of cancer research for identifying the BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes, is working to mine the research by integrating datasets from patient populations and then running analyses across time to identify genomic determinants of different variables, including response, resistance, toxicity and survival. Working closely with MD Anderson's Molecular Diagnostics Laboratory and the Institute for Personalized Cancer Therapy, the hope is to move his findings into the clinic to advance general therapeutics and precision oncology therapies, an approach that emphasizes the uniqueness of an individual's disease based on his or her genome and is considered by many to be the holy grail of clinical genomics. The key is acquiring plenty of data, which, surprisingly, may not be the easy part of the equation. "Clinical records are famously difficult to get into research databases. Some of this is for good reason, because people don't want their health records shared indiscriminately," said Gibbs. "But even if you have a situation where everyone is on board for sharing, we still run into challenges because there is so much variation in the way clinical data is collected and measured. Everyone wants to see clinical records become more harmonized and standardized, but of course the priority is physician care, so a scientist's version of how data should be aggregated isn't going to come before that." Nevertheless, the move toward collecting and analyzing troves of genetic data for patient care purposes is becoming more and more prevalent in programs throughout the Texas Medical Center. At Texas Children's Hospital, a research study called BASIC3 (Baylor Advancing Sequencing in Childhood Cancer Care) is investigating the utility of tumor and germline (familial) whole exome sequencing for children with newly diagnosed solid tumors. As the only pediatric cancer project funded by the National Human Genome Research Institute's Clinical Sequencing Exploratory Research program, the study is unique in that it is not only examining the results of the clinical testing, but also analyzing the process of gathering and disseminating genomic data to patients and their primary oncologists. "One of our primary goals for the study was to set up the logistics and infrastructure to perform clinical sequencing—to take it from a research tool to something that we can actually do for our patients," said Will Parsons, M.D., co-director of the Cancer Genetics and Genomics Program at Texas Children's Cancer and Hematology Centers and co-principal investigator of the BASIC3 study. "This includes everything from how we're going to obtain informed consent from families and explain the risks and benefits of genomic testing, to how to explain the test results to oncologists, patients and families, to how to write genomic test reports—all the practical steps, from start to finish, of performing sequencing as a clinical test." In addition to also looking at the utility of these tests in the clinical setting and how the information can be applied to both diagnostics and therapeutics for patients and their families, the study has engaged a team of ethicists and social scientists to work with the oncologists, parents and patients to evaluate their experience and preferences for the testing process. "Both the oncologists and families are providing feedback regarding important issues related to genomic testing, such as how we're explaining the results to them, what kind of things they want to learn and whether or not they are bothered by any of the other types of results one can get when doing this scale of testing," said Parsons. "Both groups are longitudinally surveyed and interviewed so that we can gain a better understanding of how we can best interact with our patients and their families and provide the most useful information possible." Ultimately, studies like these allow institutions to begin initiating prospective clinical trials using these genomic tests, a necessary next step towards evaluating the One of our primary goals for the study was to set up the logistics and infrastructure to perform clinical sequencing— to take it from a research tool to something that we can actually do for our patients. — WILL PARSONS, M.D. Co-Director of the Cancer Genetics and Genomics Program at Texas Children's Cancer and Hematology Centers

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