The Growing Case for Whole-Genome Sequencing in All Blood Cancers

Rhea-AI Summary

Illumina has demonstrated the effectiveness of Whole-Genome Sequencing (WGS) in blood cancer diagnostics through a comprehensive study. The research evaluated WGS performance in identifying variants specific to Acute Myeloid Leukemia (AML), achieving 100% sensitivity including hard-to-find mutations. The study, conducted at Illumina Laboratory Services, achieved a five-day turnaround time and demonstrated a 95% detection rate at 5% variant allele frequency with 140× coverage.

The company's WGS method utilizes their DRAGEN software and will expand Connected Insights functionality in early 2025 to include automated risk stratification for AML samples. This advancement offers a significant improvement over conventional diagnostic methods, which often require multiple tests and have detection capabilities.

Positive

• Achieved 100% sensitivity in detecting mutations, including critical FLT3-ITD variants
• Demonstrated 95% detection rate at 5% variant allele frequency
• Reduced turnaround time to 5 days compared to longer conventional testing
• Medicare approved Washington University's WGS test for blood cancers in August 2023

Negative

• None.

Insights

Medical Research Analyst

The article highlights significant advancements in Illumina's Whole-Genome Sequencing (WGS) technology for blood cancer diagnostics. Their new WGS workflow demonstrates 100% sensitivity in detecting critical mutations, including hard-to-find indels and FLT3-ITD variants, with a 95% detection rate at 5% variant allele frequency. The 5-day turnaround time represents a major improvement over conventional multi-test approaches. The upcoming Connected Insights platform expansion in early 2025 with automated risk stratification capabilities could streamline diagnostic workflows. However, the research-use-only status and implementation challenges in healthcare systems may limit immediate market impact.

Market Research Analyst

While Illumina's WGS technology shows promising clinical utility for blood cancer diagnostics, several market factors warrant consideration. Medicare's approval of Washington University's ChromoSeq WGS test in August 2023 sets a positive reimbursement precedent. The addressable market is substantial, with 187,740 Americans diagnosed with blood cancer in 2024. The consolidation of multiple tests into a single WGS workflow could drive cost efficiencies for healthcare providers. However, market adoption faces barriers including infrastructure requirements, established clinical workflows and competition from conventional diagnostic methods. The technology's positioning as research-use-only currently limits commercial potential.

NORTHAMPTON, MA / ACCESSWIRE / December 12, 2024 / Illumina
The comprehensive method provides improved detection and greater insight on the complex disease that impacts millions of people worldwide

Originally published on Illumina News Center

The Leukemia & Lymphoma Society estimates that by year end, 2024 will have seen 187,740 Americans diagnosed with a blood cancer-or about one person every three minutes.

This unfortunate statistic belies the difficulty of arriving at a diagnosis and treatment. Current conventional diagnostic workflows use multiple lab technologies, such as karyotyping, fluorescence in situ hybridization, microarrays, gene panels, and PCR testing.The process is complex, the technology is limited, and the results can be conflicting.

With unprecedented sensitivity and accuracy, whole-genome sequencing (WGS) can detect variants and biomarkers that are critical for prognosis, risk stratification, and treatment decisions.

"Sequencing technology has really improved clinical outcomes in terms of risk stratification and diagnostic decisions for cancer," says Illumina bioinformatician Weida Gong. "For acute myeloid leukemia, or AML, in particular, sequencing is essential because the mutational profile may change a doctor's treatment decisions." Some mutational patterns more significantly impact how the disease progresses, and if these mutations or abnormalities go undetected, patients suffer lower survival rates.

The standard of care for bone marrow or blood cancer patients often involves multiple tests. "Conventionally, physicians have been using karyotyping or cytogenetics to profile just the genomic abnormality for hematology patients," Gong says. Unfortunately, these methods cannot provide a high-resolution picture of the disease. Cytogenetics may only detect chromosomal aberrations larger than five megabases (5 million genetic base pairs). Hematology patients, Gong explains, can have mutations that affect just one or a few base pairs-small insertions or deletions (indels) far from the megabase scale. Standard testing misses this important information that impacts diagnosis, risk stratification, and treatment.

Last month at the American Society of Human Genetics (ASHG) annual meeting in Denver, Gong presented a poster on a study evaluating the analytical performance of WGS (limit of detection, sensitivity, specificity, and reproducibility) in identifying somatic small variants, structural variants (SV), and copy number alterations (CNA) specific to AML, in a cohort of AML patients. (Illumina coauthor Guidantonio Malagoli Tagliazucchi had just presented the same poster at the European Society for Medical Oncology annual meeting in September.)

The researchers used a combination of 23 clinical samples from collaborators at Washington University School of Medicine in St. Louis, plus a cohort of 30 AML clinical samples from Discovery Life Sciences, and more than 500 samples, including both cell lines and clinical samples, from their in-house development and optimization work with the assay. They processed these samples with Illumina DNA PCR-Free Prep, sequenced them with the NovaSeq 6000 System with S4, and used the DRAGEN version 4.2 secondary analysis heme pipeline to compare variants detected from WGS.

The demonstration study compared the data from Illumina's WGS workflow with reference sets from Washington University and Discovery Life Sciences. Overall, they found an improved and more complete picture of each tumor, and the new data provided greater insights.

"When you look at AML patients, there are mutations that have low variant allele frequency [VAF], from 5% to 20%," Gong says. "This means that if you sequence a specific location, 5% or 20% of time, you're going to see that mutation." Standard clinical methods for blood cancers sequence at only 30× or 40× coverage. The previous Washington University paper used about 60×. In their study, Gong and his coauthors sequenced at 200× coverage, which helped reveal mutations that are more difficult to find using conventional technologies such as microarrays.

"The sensitivity was 100%, including hard-to-find indels," Gong says. "There's one particular mutation that is very, very important for AML risk stratification, and that is FLT3-ITD. There are also AML specific SVs and CNAs. We were able to detect all of them from the clinical samples." The researchers also carried out a limit-of-detection study in which they were able to report a 95% detection rate for 5% VAF at a coverage of 140×. This is the same VAF percentage as the recently FDA-approved TruSight Oncology Comprehensive assay. "The fact that this assay's limit of detection is on par with TSO Comp is super, super exciting."

The study was performed at Illumina Laboratory Services in San Diego, where the workflow is end-to-end from extraction to the downstream bioinformatics pipeline. Thanks in part to this setup, they were able to achieve a total turnaround time of five days. "This is very important, especially for the case of tumor diagnosis. Time is essential," Gong says. Conventional testing is often iterative and requires multiple steps and procedures. "Some tests, like qPCR, can be very fast, returning results in two or three days-but they only look for specific mutations. And the other tests take much longer.

"WGS is definitely very sensitive and we don't need to apply multiple different technologies to profile the genetic risk for AML patients," says Gong. "Whole-genome sequencing is a one-stop shop."

Illumina has developed a tumor-only, high-coverage WGS method and bioinformatics pipeline, based on its DRAGEN software, to better characterize hematological malignancies for research use. Illumina is the only sequencing company that provides all the components to do WGS heme testing across library prep, sequencing, secondary analysis, and interpretation.

The DRAGEN heme solution is integrated with Illumina Connected Insights to prioritize, interpret, and report on key variants for clinical researchers. Connected Insights includes a powerful tool kit with integrated knowledge sources, automated variant classification, comprehensive visualizations, and extensive filtering options. In early 2025, Illumina will expand Connected Insights' functionality to include automated risk stratification for AML samples (according to World Health Organization and European LeukemiaNet guidelines for 2022), with transparent logic and evidence display. Thanks to the software's automated data transfer and analysis launch, researchers will be able to implement a "no touch" automated complete solution, from sequencing to draft research report, and enjoy new efficiencies in heme WGS analyses.

Industry leaders understand the power of WGS to provide a comprehensive genomic characterization for hematologic malignancies, well beyond what cytogenetics applications can achieve. In August 2023, Medicare approved Washington University's WGS test for blood cancers, called ChromoSeq. Yet wider implementation of WGS-even for AML, where its value has been reported-remains a challenge for health care systems.

"There is a lot of interest," Gong says. "Regarding the utility of WGS, the sky is the limit."

To learn about the Illumina heme WGS interpretation solution, click here.

To read about applications of WGS in hematologic malignancies, click here.

To see a demonstration of the DRAGEN bioinformatics pipeline for heme WGS, please contact dragen-info@illumina.com.

PHOTO: Andrew Brookes

View additional multimedia and more ESG storytelling from Illumina on 3blmedia.com.

Contact Info:
Spokesperson: Illumina
Website: https://www.3blmedia.com/profiles/illumina
Email: info@3blmedia.com

SOURCE: Illumina

View the original press release on accesswire.com

FAQ

What detection rate did Illumina's WGS achieve for blood cancer variants?

Illumina's WGS achieved a 95% detection rate for 5% variant allele frequency (VAF) at a coverage of 140×, matching the performance of their FDA-approved TruSight Oncology Comprehensive assay.

How long does Illumina's WGS blood cancer testing take compared to conventional methods?

Illumina's WGS testing provides results in five days, while conventional testing methods often require multiple steps and longer timeframes, though some specific tests like qPCR can return results in 2-3 days but only for specific mutations.

What new features will Illumina's Connected Insights add in early 2025?

In early 2025, Illumina will expand Connected Insights to include automated risk stratification for AML samples, following World Health Organization and European LeukemiaNet guidelines for 2022.

What advantage does Illumina's WGS offer over traditional blood cancer testing methods?

Illumina's WGS offers improved detection of mutations and variants compared to conventional methods like karyotyping and cytogenetics, which can only detect chromosomal aberrations larger than 5 million base pairs.