Our genomic and genetic research encompasses cancer and many other diseases. It includes studies of cancer mutations that promote therapeutic response or resistance, the evolution of the influenza and Ebola viruses and the genetics of diabetes risk across diverse populations. This work crosses multiple disciplines, including biology, chemistry and computer science, and it often involves collaborations with researchers and institutions around the globe. Our research also includes the fields of epigenetics (the study of heritable chemical modifications to DNA and its packaging that influence gene expression) and epigenomics (the study of all epigenetic modifications across the genome).
The Genetics of Disease Risk
DNA mutations are a hallmark of many cancers. For example, inherited genetic factors explain about a third of the risk of colorectal cancer. Lifestyle and environmental factors are other contributors. DNA mutations can also be acquired later in life, and some of these mutations represent good targets for new drugs.
Fred Hutch researchers have identified 40 new genetic signals that are significantly associated with risk for sporadic colorectal cancer, the most common form of the disease, as well as the first rare protective genetic variant for sporadic colorectal cancer. They are also devising models to predict individual 10-year risk for colorectal cancer based on an array of environmental, lifestyle and genetic risk factors. The individual risk levels could be used to calculate the recommended age to start screening for this cancer, for which there is currently no recommendation based on individual risk. Other Fred Hutch investigators study the epigenetic biomarkers of colon cancer and colon tissue that is at greater risk of developing into cancer, which could lead to new screening tests.
Fred Hutch serves as the coordinating center for the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), an international collaboration that uses genetic data from more than 40,000 participants. GECCO investigates the impact of common and rare genetic variants on colorectal cancer risk.
Benefits of Screening for Inherited Mutations
One Fred Hutch study found that men with metastatic prostate cancer are five times more likely than the general population to harbor inherited mutations in certain genes that keep DNA error-free, including the “breast cancer genes” BRCA1 and BRCA2. These patients could therefore benefit from screening for these mutations so they can get more tailored treatment and a clearer prognosis — as well as alert family members about their own cancer risk.
Genes and Personalized Medicine
Genetic testing is increasingly informing individualized cancer treatment. Numerous Fred Hutch investigators are contributing to this movement toward personalized genetic medicine. Our researchers study specific genetic vulnerabilities in a range of cancers, such as prostate cancer and various forms of lung cancer — including the aggressive small-cell form and lung tumors in never-smokers. They are also investigating how detailed analysis of a patient’s tumor cells can distinguish between the DNA mutations that affect cancer survival and those that don’t, which could potentially lead to more precisely tailored treatments.
Chemotherapy is known to damage DNA and can itself lead to cancer. If oncologists could measure a patient’s mutation rate from chemotherapy — as well as from innate defects and specific environmental exposures — they could potentially determine how much chemotherapy that person can withstand without raising the risk of developing a secondary cancer. This is an area of research at Fred Hutch that could have wide-ranging benefits in oncology.
Tools for Genomic Analysis
The field of genomics is evolving rapidly due to the development of more advanced tools and computational capabilities. Fred Hutch scientists are contributing to that evolution. One example of our impact is a method that accurately detects unique mutations in specific areas of the genome and is up to 1,000 times more sensitive than other approaches. The method can accurately detect a single gene carrying a hallmark cancer mutation among millions of unmutated versions of the same gene. Another example is a tool to map specific epigenetic modifications in single cells, giving researchers insights into how specific genes’ activity may be tuned.
Genomic studies involve data sets so large and diverse that analyzing them often requires entirely new methodologies. Data scientists across Fred Hutch are involved in developing statistical and computational methods and software to analyze large data sets generated by gene sequencing technologies in the study of cancer, HIV and other diseases. They include researchers who are helping to develop computational tools for the Human Cell Atlas, a global research effort to map every type of cell in the human body, and data scientists who are developing methods to detect cancer-specific genomic alterations in blood samples.
