Since the mapping of the human genome — all of the DNA within a human cell — was completed in 2003, research into the genetic factors behind health and disease has exploded, leading to revolutionary new therapies as well as more personalized, targeted treatments for cancers and other diseases. This expanding area of knowledge and growing data sets are leading to improved diagnosis and prevention. At Fred Hutch, DNA sequencing and genetic epidemiology are critical aspects of our basic and clinical research.
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).
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.
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.
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.