Using WGS to Improve Genomic Profiling in Patients With Blood Cancers

Whole-genome sequencing (WGS) is at least as accurate as conventional tests when it comes to genomic profiling in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Potentially, WGS could replace conventional cytogenetic and sequencing approaches, according to a study in The New England Journal of Medicine.

While genetic profiling is routinely used to predict outcomes and responses to certain therapies in an increasing number of cancers, mutations can span a wide range of genomic events, which requires the use of multiple platforms to obtain the necessary information. However, WGS can be used to detect all types of mutations.

“Choosing the appropriate therapy for cancer patients often depends on identifying a range of different types of genetic changes in a patient’s tumor cells,” senior author David H. Spencer, MD, PhD, an assistant professor of medicine and medical director of the clinical sequencing facility at the McDonnell Genome Institute at Washington University School of Medicine in St. Louis, said in a statement. “Our study suggests whole-genome sequencing is a reliable and practical approach for detecting all of the changes that are important for assessing the risk of relapse for AML and MDS patients, using a single test.”

The researchers obtained genomic profiles for 263 patients with myeloid cancers, 235 of which had undergone successful cytogenetic analysis. Using WGS, they were able to detect all 40 recurrent translocations and 91 copy-number alterations that the cytogenetic analysis identified. In 40 of the 235 patients, they also identified additional genetic abnormalities.

Of the full cohort, 117 patients were newly diagnosed, while the other patients’ samples were being analyzed retrospectively. In newly diagnosed patients, the WGS found additional genetic information in about one-fourth of the cases. The new information resulted in 19 patients being recategorized for risk, which could change their treatment options.

In addition, WGS was used to risk stratify patients who previously had inconclusive results.

“Inconclusive results are extremely frustrating, because we want to be able to offer patients the most appropriate treatment at the beginning of therapy,” Timothy J. Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Medicine at Washington University School of Medicine in St. Louis, said in a statement.

The authors noted that the cost of WGS was similar to the estimated cost range for conventional methods. Costs for current testing can be between $1000 and $2000 and the cost for WGS as the authors used it in the study was approximately $1900. The cost could be as low as $1300 in high-volume laboratories with lower sequencing costs, but the actual charge would probably be higher due to other costs association with implementation.

“Implementing whole-genome sequencing for clinical testing can provide a unified, stable, and extensible platform that minimizes laboratory-specific bias and that can be standardized throughout the world,” the authors concluded. “Although our study focused on myeloid cancers, many of the advantages of whole-genome sequencing that we observed will directly apply to patients with other cancers.”

Reference

Duncavage EJ, Schroeder MC, O’Laughlin M, et al. Genome sequencing as an alternative to cytogenetic analysis in myeloid cancers. N Engl J Med. 2021;384:924-935. doi:10.1056/NEJMoa2024534