While the study’s results indicated whole-genome sequencing didn’t always have predictive power in early cancer detection, there was still value in genetic risk assessment in cases where pathogenic variants and nodules of unknown pathogenicity were detected simultaneously. Robyn Heister, MD, a physician at HLI and a coauthor on the study, described the example of a female participant with a thyroid nodule detected with deep phenotyping. Along with the observable nodule, whole-genome sequencing also revealed the patient had a germline pathogenic RET variant, an oncogene commonly implicated in the development of papillary thyroid cancer.3
Dr Heister described how the patient was “initially reluctant to do an ultrasound,” a commonly used follow-up screening method when thyroid nodules are detected. But, said Dr Heister, “the genetic findings made it easier to help her (the participant) understand it was worth the trouble of getting the appropriate follow-up testing,” showing the utility of both deep phenotyping and whole-genome sequencing in guiding patient decisions when informed of genetic risk.
Dr Heister also described the importance of whole-genome sequencing in identifying novel familial variants, which are inherited through the germline. “In addition, in my opinion, there’s huge value to [a patient’s] family members to understand that they might also benefit from testing for this oncogene,” pointing to the important observation of the ability of whole-genome sequencing to identify novel inherited risk variants in the general population that are commonly implicated in cancer development. In this case, establishing the importance of testing the participants’ family members for the pathogenic RET variant, in the same way BRCA testing is used in breast cancer or MSH6 in Lynch syndrome.
So, while the study didn’t necessarily show predictive value of whole-genome sequencing in early cancer detection, it still showed clinical utility in assessing genetic risk, and that risk information was used to inform both physician and patient decisions. Plus, the study revealed novel inherited pathogenic variants in the general population. “Our study showed that by employing a holistic and data-driven health assessment for each individual, we are able to achieve early disease detection in adults,” C. Thomas Caskey, MD, chief medical officer for HLI, said in an HLI press release.2
“This study shows that the definition of ‘healthy’ may not be what we think it is and depends upon a comprehensive health evaluation,” added J. Craig Venter, founder of HLI and a pioneer of many well-known genomic ventures, in a press release.2
According to Dr Hou, future goals of HLI’s work in early cancer detection, specifically, include integration of liquid biopsy and other somatic testing methods into the Health Nucleus platform. And in the longer term, HLI plans to enroll larger numbers of participants in longitudinal studies to further refine their methods of early disease and cancer detection.
- Claire Hou Y-C, Yu HC, Martin R, et al. Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. PNAS. 2020;117(6):3053-3062.
- Feinberg, Debbie. Human Longevity’s largest study of its kind shows early detection of disease and disease risks in adults [press release]. Published January 27, 2020. Accessed April 3, 2020.
- Jhiang SM. The RET proto-oncogene in human cancers. Oncogene. 2000;19(49): 5590–5597.
This article originally appeared on Cancer Therapy Advisor