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Whole-Genome Sequencing for Genetic Profiling in Myeloid Cancers

By: Vanessa A. Carter, BS
Posted: Wednesday, May 19, 2021

David H. Spencer, MD, PhD, of Washington University School of Medicine, St. Louis, and colleagues evaluated the accuracy, utility, and feasibility of whole-genome sequencing in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes. These researchers discovered that whole-genome sequencing was, in fact, beneficial in determining gene profiles, perhaps representing an alternative to cytogenetic analysis, and their results were published in The New England Journal of Medicine.

“In our study, we found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or myelodysplastic syndromes,” the study authors concluded. “Such sequencing also provided a greater diagnostic yield than conventional cytogenetic analysis and more efficient risk stratification on the basis of standard-risk categories.”

Streamlined whole-genome sequencing was performed on 263 patients with myeloid cancers; 235 underwent successful cytogenetic analysis. Samples were obtained from peripheral blood and fresh bone marrow specimens. Fluorescence in situ hybridization, chromosomal microarray, RNA sequencing, and polymerase chain reaction was used to confirm whole-genome sequencing findings that may not have been revealed by cytogenetic analysis.

This analysis yielded a mean genome coverage of 50x, and a mean of 5.1 clinically relevant mutations was identified per patient. All 91 copy number alterations and 40 recurrent translocations detected by the cytogenetic analysis were also identified by whole-genome sequencing. In 40 patients, new, clinically reportable genetic events were detected, according to the authors.

Additionally, new genetic information was discovered in 29 of 117 patients who underwent prospective sequencing, altering the risk category for 19 of these patients. Of note, it was found that risk predictions based on whole-genome sequencing correlated with outcomes, demonstrating a shorter median overall survival in 6 patients with adverse risk (3.3 months) than in 21 patients with intermediate or favorable risk (20.5 months).

Disclosure: For full disclosures of the study authors, visit nejm.org.


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