The future of genetic testing


Until recently, cancer genetic testing was based on inspection of a few genes, but laboratories are now able to look at a patient’s entire genome, which includes approximately 20,000 genes and the intervening sequences. This is the future of genetic testing and the next revolution in cancer care.

Many families have a history of cancer in which the disease looks hereditary but the genetic etiology is unknown. Recently, members of Dr. Theodora Ross’s lab worked with the Cancer Genetics clinic and used germline whole genome sequencing (WGS) to study 278 cancer patients who had family histories of cancer. The researchers performed whole-genome testing on two cohorts of patients, those with BRCA1/ BRCA2 mutations (n=176) and those without (n=82). Using WGS, researchers were able to identify potentially pathogenic mutations in 21 percent of the latter patient population.

This study illustrates how WGS can be used to improve our ability to discover patients’ cancer genetic risks. Also with this study population, the research group demonstrated how known deleterious BRCA1/BRCA2 missense mutations are hidden behind large numbers of new, private variations observed in BRCA1/ BRCA2 genes. This illustrates how big data can hide key data.

Not only did researchers discover loss-of-function mutations in novel genes, which could explain the family histories of cancer, they have used these data to advocate for an FDA mandate in which sharing of clinical sequence data by testing laboratories becomes a standard of clinical care. In fact, the study’s organizers have deposited all of the clinical and sequence data from this WGS study into the National Institute of Health’s repository of research sequences for researchers around the country to use, and the group will continue to make such deposits in future studies of patients’ genomes. For more information, see Foley et al., 2015 EBioMedicine.

Genetic counselors at UT Southwestern collaborate with other disease-oriented teams within the Simmons Comprehensive Cancer Center to use data from these clinical services to expand the field of cancer genetics. For example, the Cancer Genetics team’s partnership with the UT Southwestern Breast Imaging Department and Breast Center has resulted in the analysis of 96,055 individuals at screening mammography for a family history of cancer to identify BRCA mutation carriers who have a genetic predisposition to breast and ovarian cancer. This is the largest study to date on this topic. As a result of this screening program’s success in identifying high-risk individuals and completion of cancer prevention activities, the Cancer Genetics team was able to work with Dr. Xian-Jin Xie from the Department of Clinical Sciences to create a computer model for quantifying cancer prevention. This model can now be used for future screening programs— not only to identify those at high genetic risk but also to make the results beneficial for large populations. For more information, see Robinson et al., 2015 EBioMedicine.

Even as the cancer genetics community moves to next-generation sequencing of multiple genes in the genetics clinics, UT Southwestern was one of the first groups to publish its experience with multi-gene panel testing and the implications of clinical care (Mauer et al., 2013 Genetics in Medicine; Yorczyk et al., 2014 Clinical Genetics). After confirming with data that different testing laboratories were interpreting the same genetic changes differently, the Cancer Genetics team made its proposal to the FDA that data sharing should be part of genetic testing (Ross, 2014 NYTs; Ross, 2015 Cold Spring Harb Mol Case Stud).

The UT Southwestern team is continually collaborating, both internally and externally, to find the missing pieces in the cancer genetic story.