Team

Genetic testing can be an important tool in helping patients learn about their inherited cancer risk, but the results are not always as clear as patients might expect. Just as traits such as hair color and eye color can be passed down from parents to their children, so too can the risk for developing certain types of cancer. Scientists know that certain inherited gene mutations — small changes in a person’s DNA — can increase a person’s risk for developing diseases such as breast cancer, ovarian cancer, and colon cancer. Genetic testing examines a person’s DNA to determine if such mutations are present, helping patients better understand their cancer risk and, in some cases, allowing them to take charge of their health before receiving a devastating diagnosis. Understanding the Basics of Genetic Testing Only five to 10 percent of all cancers are believed to be tied to an inherited gene mutation.1 Genetic testing can help determine whether an individual has inherited a specific gene mutation (or mutations) that put him or her at higher risk for developing certain cancers. Most genetic tests require a small blood sample from the patient, but some tests can be performed using urine, saliva, or a cheek swab. The sample is sent to a special laboratory and results are usually provided to the patient’s doctor or genetic counselor within several weeks.2 Genetic testing can return one or a combination of the following results: Positive: The laboratory identified a genetic mutation that is associated with an inherited cancer risk.2 Negative: The laboratory did not find the specific genetic mutation (or mutations) that the test was designed to detect.2 Inconclusive: The laboratory was not able to determine whether a specific genetic mutation (or mutations) was present in the sample provided.2 Variance of Uncertain Significance: The laboratory identified a genetic mutation that has not been previously associated with cancer.2 No test can provide exact answers about a person’s inherited cancer risk. Genetic testing can tell you whether a specific genetic mutation is present in your DNA, but it cannot tell you for certain that you will develop the disease associated with that mutation later in life.3 Knowing Your Cancer Risk: Is Genetic Testing Right for You? Doctors often only recommend genetic testing for patients whose families have a history of certain cancers or patterns of cancer. According to the American Cancer Society, people who meet the following criteria might consider genetic testing: Cancer diagnoses in multiple first-degree relatives, including parents, siblings, or children1 Numerous relatives on one side of the family who have been diagnosed with the same cancer1 Family history of cancers linked to a single gene mutation, such as breast cancer, ovarian cancer, or pancreatic cancer1 Family member(s) who has been diagnosed with more than one type of cancer1 Family member(s) who has been diagnosed with cancer at a younger age than typically seen for that cancer, such as colon cancer1 Close relatives who have been diagnosed with cancers linked to rare hereditary cancer syndromes, such as Hereditary Breast & Ovarian Cancer Syndrome (HBOC), Cowden Syndrome, or Lynch Syndrome1 Family member(s) who has been diagnosed with […]

“The essence of precision medicine, in particular precision oncology, is to make cancer management more precise based on genomic mapping and molecular characterization of the unique tumors for each patient,” says Dr. Wei Zhang. “The cancer management that needs to be precision include diagnosis, prognosis, treatment plan, treatment monitoring, and genetic counseling.” Precision medicine, and by extension, oncology, is the buzzword of the moment among doctors and researchers, and it is more than just spin or a fad. With regards to cancer, and as our understanding of the disease has increased, the idea of a one-drug-cures-all panacea is now widely considered obsolete (however much of a holy grail such would be). Cancer, even the same type, varies at a genetic level from patient to patient. The therapies that work with “Patient A” may not at all with “Patient B,” due at least in part in the natural genetic difference that exists among practically all living things. Zhang admits the field is still in its infancy, the promise it holds is vast: with the rise of genomics, scientists can untangle the genetic knot of cancer, tailoring customized treatment regimens unique to a person, start to finish. Trailblazing cancer research for the last 20 years, Zhang has been witness to the evolution of cancer treatment, at one point co-directing a Genome Data Analysis Center under the National Cancer Institute-funded Cancer Genome Atlas program. He also served as Director of the Cancer Systems Biology Center funded by the National Foundation for Cancer Research for several years when at the MD Anderson Cancer Center. In 2016, he was recruited to the Wake Forest Comprehensive Cancer Center located in Winston Salem, North Carolina to lead the Center for Cancer Genomics and Precision Oncology and takes a direct role in the development of targeted therapies. Moreover, Zhang, who is also an NFCR Fellow, instituted sorely-needed diversity in cancer research. While cancer is not particularly picky, some forms of it tend to show up more in specific ethnicities that, historically, were overlooked, often with great detriment: African-Americans have the highest death rate and shortest survival of any racial and ethnic group in the USA for most cancers. “Our precision medicine/oncology considers health disparities a priority issue of our cancer center,” Zhang explains. “In our program, 14 percent of all cancer patients who are enrolled in our precision oncology trials are African-American patients, a percentage that is much higher than most cancer centers in the country. We have taken on a leading role in our effort in understanding the unique genomics features for cancer of African-American ancestry.” For all its promise, Zhang stressed that precision medicine, and oncology, is still in its infancy. The single most rate-limiting challenge is the effective matching of genomic mutations with corresponding drugs. That being said, precision medicine/oncology is for everyone involved in cancer management. That includes patients and family members, doctors, researchers, pharmaceutical companies, funding agencies and insurance industries.  Decisions have to be made through better research and better development of targeted therapeutics. Zhang is optimistic. “The efficacy will continue to improve with the effort of national consortium such as Precision Medicine […]

Genomics, the branch of molecular biology concerned with the structure, function, evolution, and mapping of an individual’s genes, is already revolutionizing the way medicine treats cancer. Like many sciences, genomics has “niches;” single-cell genomics is a rapidly developing field, and current technologies can assay a single cell’s gene expression, DNA variation, epigenetic state, and nuclear structure within its environment. Cellular identity is critical by itself; the human body is composed of trillions of cells that belong to approximately 200 different cell types and even those types are, from cell to cell, filled with unique expression profiles. When cancer is involved, a disease that deals in very specific chain of events, it becomes even more so. Heralded as “Breakthrough of the Year” by Science Magazine in 2018, single-cell sequencing, which, as the name implies, involves isolating a single cell for analysis, gives insight into what had been insurmountable obstacles. Heterogeneous samples, rare cell types, cell lineage relationships (including back-engineering cells all the way back to the zygote stage of pregnancy), analyses of microbes that cannot be cultured, and disease evolution can now be explored. With cancer, the process can be used to explore why some tumor cells react to chemotherapy, others do not and live on to spread. Traditional sequencing techniques such as the Sanger or Illumina processes usually use a mix of cells numbering in the millions. The results are a genomic “big picture” where the finer points are skipped (this is not a negative; both techniques have saved thousands of lives and opened up venues to cancer cures unthinkable 20 years ago). The first single-cell RNA-sequencing study was published in 2009; the technique is now positioned to reveal cancer therapy resistance mechanisms that are lost at the bulk level. Tumors diverge wildly from cell to cell, and that diversity is impacted by selection pressures that can impact the underlying genetics of a cancer cell population. Selection pressures represent a wide spectrum of factors, including the effects of the immune system, hypoxia (lack of oxygen), nutrient deprivation, geographical barriers, pH changes, and chemotherapy. NFCR is fully involved in this technology by funding the work of Dr. Haiyong Han and Dr. Daniel Von Hoff of the Arizona-based Translational Genomics Research Institute. The two are using single-cell sequencing on pancreatic cancer biopsy tissue from patients and tumor models. By performing single cell sequencing, Han and Von Hoff hope to find new targets in the stroma (the supporting structure around a tumor), EMT cells (cells that gain migratory and invasive properties) and treat patients in a pilot clinical trial for precision medicine. With the advent of drastically cheaper and higher throughput sequencing technologies, it is expected that single cell sequencing will become a standard tool in oncology and microbiology. References: ACloserLookAtStemCells.org. (2019). Single Cell Sequencing: Unwinding Embryonic Development One Cell at a Time. Retrieved from: https://www.closerlookatstemcells.org/2019/01/04/single-cell-sequencing-unwinding-embryonic-development-one-cell-at-a-time/ Haque, Ashraful. (2017). A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications. Retrieved from: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0467-4 Yilmaz, Suzan et al. (2012). SINGLE CELL GENOME SEQUENCING. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318999/