Three hot topics from AACC’s journal Clinical Chemistry were featured in a symposium on Wednesday afternoon. Nader Rifai, PhD, Clinical Chemistry Editor-in-chief, selected these topics and moderated the session. “I felt that these are three of the most interesting areas we addressed in the journal in the past year,” Rifai said. “They have great diagnostic and prognostic potentials. Certainly, they force us to challenge existing practices.”
Dennis Lo, MD, PhD, spoke first about plasma genomic and methylomic sequencing for cancer detection. The cancer genome is characterized by a number of molecular aberrations, including amplifications and deletions—copy number aberrations—and DNA methylation aberrations. Lo’s method uses genome-wide sequencing of plasma DNA to identify copy number aberrations and DNA methylation abnormalities due to cancer. His group has developed this technology alongside their development of similar technologies for fetal genome and epigenome sequencing.
“This technology has implications for cancer detection, monitoring, and prognostication,” Lo said. “It is also potentially applicable to virtually all cancer types. We have shown that it is applicable for hepatocellular carcinoma, breast cancer, lung cancer, certain sarcomas, neuroendocrine tumors, nasopharyngeal cancer, and others.”
Ravi Thadhani, MD, discussed bioavailable vitamin D in the second presentation. Measurement of vitamin D has increased dramatically over the past 5-10 years, not only for the assessment of bone disease, but also for risk of a variety of chronic diseases including heart disease, cancer, and diabetes. However, association data between vitamin D concentration and these chronic diseases have not been consistent. Furthermore, there have been some unexplained observations, such as the low concentration of vitamin D in blacks compared to whites that is not accompanied by a high incidence of fractures.
In a landmark report, Thadhani and his colleagues raised the question of whether bioavailable, rather than total, vitamin D should be measured, thus casting a doubt on all association studies that have been done (NEJM 2013; 369:1991-2000). This concept was highlighted in Clinical Chemistry in Perspective and Q&A articles. “The concept is one ‘borrowed’ from other hormones,” said Thadhani. “If vitamin D behaves under similar principles, then bioavailable or that loosely bound to albumin and that which circulates free (< 1%) is what delivers vitamin D to cells. Our early studies suggest this is important, especially in individuals with genetic polymorphisms linked with vitamin D binding protein that are often associated with low total vitamin D levels.” These findings potentially change our understanding of the prevalence of vitamin D deficiency, and more importantly, whom to target for therapies. However, Thadhani cautions that more research is still needed.
In the final talk, Marilyn Huestis, PhD, discussed the use of oral fluid (OF) for drug testing. Huestis has been a pioneer in studying the pharmacodynamics and pharmacokinetics of drugs of abuse after controlled drug administration, and in identifying the best biological matrices in which to measure them. Currently, urine and blood are the most common matrices for drug testing. OF is attractive as a testing matrix because collection is non-invasive and directly observed—important for reducing specimen adulteration.
Huestis’s laboratory also has studied the detection of cannabinoids, cocaine, MDMA, methamphetamine, amphetamine, opiates, buprenorphine, and methadone in OF. OF offers roadside testing for drugs of abuse as drugged driving is a major public health and safety problem, with 8.5% of nighttime drivers being positive for a cannabinoid marker. However, Huestis cautions that many questions still remain about the disposition of drugs and metabolites in OF, as well as windows of drug detection, and appropriate OF cutoffs. Despite many unanswered questions, OF testing is clearly a promising new matrix for drug testing.