Whole-genome sequencing makes a case in the study of leukemia

Whole genome sequences (WGS) provided more information on the genetics of myeloid malignancies and altered the risk category in 16% of patients compared with conventional cytogenetic analysis.

WGS identified all of the transplants and changes in copy number detected by cytogenetic analysis as well as 40 additional anomalies in 235 patients. In a prospective evaluation involving 117 follow-up patients, WGS provided new genetic information in a quarter of patients, and the median wait for results was 5 days.

Risk groups defined by WGS were linked to clinical outcomes, and patients at risk of WGS with uncertain cytogenetic outcomes, reported David H. Spencer, MD, PhD, University of Washington at St. Louis. Louis, and colleagues in the New England Journal of Medicine.

“We found that whole-genome sequencing provided fast and accurate genomic counts in patients with AML [acute myeloid leukemia] and MDS [myelodysplastic syndromes], “they said.” Such classification also provided greater diagnostic results than conventional cytogenetic analysis and more efficient risk stratification on the basis of standard risk categories. “

WGS may be cost-competitive with cytogenetic analysis and is suitable for a wide range for malignancies.

“Implementing whole-genome sequences for clinical trial can provide a unified, stable and scalable platform that reduces specific laboratory bias and can be normalized worldwide,” they said. . “While our study focused on myeloid cancers, many of the benefits from whole-genome classification we have seen will directly apply to patients with other cancers.”

Tumor genetics analysis has become a routine part of the research work for a growing number of cancers. However, clinically workable mutations surround a wide range of genomic events, which require several platforms to obtain genetic information for clinical management, Spencer and colleagues noted.

WGS offers a neutral method to detect all types of mutations and could replace the standard test methods, they continued. The sequence requires little DNA and can identify genomic changes that may rule out other types of analysis. Taken together, the benefits of WGS suggest the potential for improving the genomic image of patients with cancer.

Historically, WGS has been time consuming and costly, limiting the technology to research scenarios, the Spencer group acknowledged. Recent technological advances have simplified the analysis process and made it faster and cheaper.

To investigate the potential of WGS for routine analysis of patients with cancer, researchers developed a rapid approach to WGS for patients with AML or MDS. They analyzed clinical samples in real time to assess the feasibility, accuracy and feasibility of WGS in the clinical setting.

The scalable method involved the use of scalable methods of sample preparation performed within 8 hours by a single technologist, using commercially available feedback, followed by a standard high-throughput series. . Analysts used automated tumor analysis only to detect mutations in selected genes, changes in copy number of more than 5 megabase pairs, and recursive structural changes.

WGS was used to examine samples from 235 patients with confirmed or suspected hematologic cancers. Previous cytogenetic analysis had identified 91 changes in copy number and 40 repetitive regression. WGS identified all of these disorders and 40 clinically reported new genomic events, resulting in 17% of patients having results not detected by conventional cytogenetics.

To examine the feasibility of routine use of WGS in clinical oncology practice, researchers evaluated 117 follow-up patients. WGS was performed weekly in glasses of one to 11 samples (bone marrow aspirator). The average time required for processing was 5.1 days. Seven samples required manual revision of automation, but the remaining 110 did not require any additional intervention to produce a final series report.

WGS provided new genetic information in 29 (24.8%) of the 117 patients, and the new information led to a change in risk category for 19 (16.2%) patients. Risk groups were defined by WGS outcomes linked to clinical outcomes.

The authors estimated that the cost of WGS, as estimated in their study, was approximately $ 1,900, placing it in the range of other test platforms. At high-throughput labs the cost could be around $ 1,300. As the cost of sequencing decreases, WGS is likely to reach price parity with conventional test platforms.