Whole-genome sequencing was found to provide rapid and accurate genomic profiling for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), and this technology may be a potential replacement for conventional cytogenetic and sequencing approaches to risk stratification, according to the results of a study published in the New England Journal of Medicine.

“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,” study researchers stated. “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,” the researchers concluded.

Patients who have AML or MDS often undergo genetic profiling for diagnostic classification and risk assessment. This study tested whether whole-genome sequencing could be streamlined and applied to diagnostic clinical samples in real time. The study included genomic profiles from 263 patients with myeloid cancers, including 235 who had undergone cytogenetic analysis.

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In this study, whole-genome sequencing identified all 40 recurrent translocations and 91 copy-number alterations that were detected using cytogenetic analysis. In addition to these mutations, whole-genome sequencing identified new clinically reportable genomic events in 40 of the 235 patients (17%).

Prospective sequencing was performed on samples taken from 117 consecutive patients in a median of 5 days. These 5 days included 2 days for library preparation, 2 days for sequencing, and less than 1 day for analysis. Results provided new genetic information in 29 patients (24.8%), and risk category changed in 19 patients (16.2%).

According to the researchers, risk prediction based on the whole-genome sequencing results correlated with outcomes. Significantly longer overall survival was observed in the 21 patients with intermediate or favorable risk compared with the 6 patients with adverse risk.

“This survival difference was superior to that resulting from the assignment of patients to risk groups on the basis of gene mutations alone,” the researchers noted. “Although larger studies involving more patients will be required to firmly establish the clinical

performance of whole-genome sequencing, our proof-of-concept study shows that this method has the potential to add prognostic value by expanding risk stratification to more patients, especially for those with inconclusive results on cytogenetic analysis, where whole-genome sequencing could have an immediate effect on treatment decisions.”

Disclosure: Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.


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