Whole genome sequencing outperforms cytogenetic analysis in myeloid cancers

March 2021 Science Tobias Rawson
Dna test infographic. Genome sequence map, chromosome architecture and genetic sequencing chart abstract data. Molecule structure genetic test. Genealogy sequence vector illustration

For patients with acute myeloid leukaemia or myelodysplastic syndromes, genomic analysis enables risk stratification, and has become an essential tool in the management plan of these patients. Whole-genome sequencing (WGS) is a potential replacement for conventional cytogenetic and sequencing methods currently used. However, the accuracy and overall clinical utility of WGS had not been demonstrated in these haematological settings until recently. 

Reported in the New England Journal of Medicine, a team of researchers have demonstrated the superiority of WGS over conventional methods. The study enrolled 263 patients with myeloid cancers to undergo whole genome sequencing, 235 of which had also undergone cytogenetic analysis. Results of the two methods were then compared directly, and risk stratification using both methods was commenced and compared.

Additional genetic information in 17% of patients with WGS

In this study, WGS was able to detect all 40 recurrent translocations and 91 copy-number alterations. Furthermore, additional, clinically relevant genomic events were detected in 17.0% of patients (N= 40) with WGS. Prospective sequencing of 117 patients also demonstrated the clinical utility of WGS, as WGS was able to provide additional genetic information in 24.8% (N= 29) of these patients, with 16.2% (N= 19) of these patients having their risk category changed as a result. Risk stratification with WGS was also correlated with clinical outcomes. WGS was also used to complete the risk stratification for patients who had incomplete or inconclusive genetic profiling with conventional methods.

Overall, this study was able to demonstrate the superiority of WGS over conventional genetic profiling methods in the setting of acute myeloid leukaemia and myelodysplastic syndrome. Specifically, the use of WGS was able to provide accurate and additional genetic information in a timely manner which corresponded with risk stratification and clinical outcomes, demonstrating the clinical utility of WGS in this haematological setting.


Duncavage EJ et al., Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. New Eng J Med. 2021; 384(10): 924-935.