G2 Insider: Study Finds Hurdles Persist for Clinical Use of Whole-Genome Sequencing

While clinical whole-genome sequencing (WGS) is being employed by early clinical adopters, it may still not be ready for prime time, especially for prediction of disease risk, according to a small study published March 12 in the Journal of the American Medical Association. Challenges include both technical issues and the “considerable” human resources needed for clinical interpretation that remains rather subjective. Stanford University researchers conducted WGS in 12 adult patients (seven women; five white and seven East Asian). Coverage and consistency of clinically relevant genetic variation were evaluated between sequencing systems (San Diego-based Illumina and Mountain View, Calif.-based Complete Genomics). Agreement of interpretation was evaluated both for potentially reportable genetic findings and proposed clinical follow-up. The researchers found that reportable genes associated with inheritable conditions were commonly not covered at adequate standards (10 percent for Illumina and 19 percent for Complete Genomics) and would thus require supplementation with other genetic assays. Genotype concordance was high (99 percent) for previously described single nucleotide genetic variants, but low for small insertion or deletion variants that can be clinically meaningful (53 percent to 59 percent). For each participant, 90 to 127 genetic variants of potential personal risk and carrier status were identified and required a median of 54 minutes of investigation per variant, making the median cost for sequencing and variant interpretation $14,815 (not including costs of computing infrastructure and data storage). Two to six personal disease-risk findings were reported in each participant, including one frameshift deletion in the BRCA1 breast cancer gene in a woman with no known family history. Physician review of sequencing findings prompted consideration of a median of one to three initial diagnostic tests and referrals per participant, ranging in cost from $351 to $776. “We need to be very honest about what we can and cannot do at this point in time,” Euan Ashley, M.D., a senior study co-author, said in a statement. “It’s clear that if we sequence enough cases, we can change someone’s life . . . Our hope is that the identification of specific hurdles will allow researchers in this field to focus their efforts on overcoming them to make this technique clinically useful.” For more information on the clinical adoption of next-generation sequencing (NGS), don’t miss G2’s conference, MDx NEXT, which will be held June 11-13 in Baltimore (www.mdxconference.com). Sherri Bale, Ph.D., FACMG, managing director of GeneDx and senior vice president of Bio-Reference Laboratories, will be discussing challenges ahead for NGS. Kevin Davies, founding editor of Nature Genetics and Bio-IT World and author of The $1,000 Genome, will address the $1,000 genome and beyond.