Revolutionizing Blood Cancer Diagnosis with Whole-Genome Sequencing
The Leukemia & Lymphoma Society projects that by the end of 2024, approximately 187,740 Americans will be diagnosed with blood cancer, equating to about one new case every three minutes. This statistic highlights the complexity of diagnosing and treating these conditions. Traditional diagnostic methods rely on several laboratory techniques, including karyotyping, fluorescence in situ hybridization, microarrays, gene panels, and PCR testing. These approaches are often intricate, technologically limited, and can yield conflicting results.
Whole-genome sequencing (WGS) offers an unprecedented level of sensitivity and accuracy, enabling the detection of crucial variants and biomarkers for prognosis, risk assessment, and treatment decisions. "Sequencing technology has greatly enhanced clinical outcomes, particularly in cancer risk stratification and diagnosis," says Weida Gong, a bioinformatician at Illumina. "For acute myeloid leukemia (AML), sequencing is vital, as it can alter treatment decisions based on the mutational profile." Certain mutations have a significant impact on disease progression, and if missed, they can lead to poorer survival rates.
Bone marrow and blood cancer patients often undergo multiple tests as part of their standard care. Gong notes that traditional methods like karyotyping or cytogenetics focus on detecting larger chromosomal abnormalities, missing smaller mutations that could be crucial for diagnosis and treatment. These conventional methods may fail to identify mutations that involve small base pair changes, which can be key in understanding the disease.
At the American Society of Human Genetics (ASHG) annual meeting in Denver, Gong presented a study on the performance of WGS in detecting small somatic variants, structural variants (SV), and copy number alterations (CNA) specific to AML. The research, which included 23 clinical samples from Washington University School of Medicine and 30 AML samples from Discovery Life Sciences, as well as over 500 additional samples, demonstrated that WGS provides a more comprehensive and accurate picture of each tumor.
"In AML patients, mutations with low variant allele frequencies (VAF), ranging from 5% to 20%, are critical," Gong explains. "If sequencing is done at lower coverage, these mutations may go undetected." Traditional sequencing methods typically operate at 30× or 40× coverage, whereas Gong's study used 200× coverage, significantly improving the detection of mutations that conventional technologies miss. The study achieved 100% sensitivity, even for hard-to-find insertions and deletions (indels), and detected critical mutations like FLT3-ITD, which is important for AML risk stratification.
In addition, the study found that WGS can detect variants at 95% sensitivity with a 5% VAF at 140× coverage, comparable to the recently FDA-approved TruSight Oncology Comprehensive assay. This ability to detect low-frequency mutations quickly is a key advantage of WGS, as traditional testing often involves multiple steps and takes longer to deliver results.
Illumina has developed a high-coverage WGS method and bioinformatics pipeline specifically for hematological malignancies, enabling faster and more efficient genomic profiling. This approach offers a comprehensive solution for researchers, integrating sequencing, secondary analysis, and interpretation. In early 2025, Illumina will enhance its Connected Insights platform to include automated risk stratification for AML, further improving efficiency and accuracy in clinical research.
While WGS has shown its potential in improving the characterization of hematological cancers, its widespread adoption faces challenges within healthcare systems. Nevertheless, industry leaders recognize the transformative power of WGS, and there is growing interest in its use for blood cancer diagnosis and treatment. "The potential for WGS is limitless," says Gong.
Click here to know more about the Illumina heme WGS interpretation solution.
Whole-genome sequencing (WGS) offers an unprecedented level of sensitivity and accuracy, enabling the detection of crucial variants and biomarkers for prognosis, risk assessment, and treatment decisions. "Sequencing technology has greatly enhanced clinical outcomes, particularly in cancer risk stratification and diagnosis," says Weida Gong, a bioinformatician at Illumina. "For acute myeloid leukemia (AML), sequencing is vital, as it can alter treatment decisions based on the mutational profile." Certain mutations have a significant impact on disease progression, and if missed, they can lead to poorer survival rates.
Bone marrow and blood cancer patients often undergo multiple tests as part of their standard care. Gong notes that traditional methods like karyotyping or cytogenetics focus on detecting larger chromosomal abnormalities, missing smaller mutations that could be crucial for diagnosis and treatment. These conventional methods may fail to identify mutations that involve small base pair changes, which can be key in understanding the disease.
At the American Society of Human Genetics (ASHG) annual meeting in Denver, Gong presented a study on the performance of WGS in detecting small somatic variants, structural variants (SV), and copy number alterations (CNA) specific to AML. The research, which included 23 clinical samples from Washington University School of Medicine and 30 AML samples from Discovery Life Sciences, as well as over 500 additional samples, demonstrated that WGS provides a more comprehensive and accurate picture of each tumor.
"In AML patients, mutations with low variant allele frequencies (VAF), ranging from 5% to 20%, are critical," Gong explains. "If sequencing is done at lower coverage, these mutations may go undetected." Traditional sequencing methods typically operate at 30× or 40× coverage, whereas Gong's study used 200× coverage, significantly improving the detection of mutations that conventional technologies miss. The study achieved 100% sensitivity, even for hard-to-find insertions and deletions (indels), and detected critical mutations like FLT3-ITD, which is important for AML risk stratification.
In addition, the study found that WGS can detect variants at 95% sensitivity with a 5% VAF at 140× coverage, comparable to the recently FDA-approved TruSight Oncology Comprehensive assay. This ability to detect low-frequency mutations quickly is a key advantage of WGS, as traditional testing often involves multiple steps and takes longer to deliver results.
Illumina has developed a high-coverage WGS method and bioinformatics pipeline specifically for hematological malignancies, enabling faster and more efficient genomic profiling. This approach offers a comprehensive solution for researchers, integrating sequencing, secondary analysis, and interpretation. In early 2025, Illumina will enhance its Connected Insights platform to include automated risk stratification for AML, further improving efficiency and accuracy in clinical research.
While WGS has shown its potential in improving the characterization of hematological cancers, its widespread adoption faces challenges within healthcare systems. Nevertheless, industry leaders recognize the transformative power of WGS, and there is growing interest in its use for blood cancer diagnosis and treatment. "The potential for WGS is limitless," says Gong.
Click here to know more about the Illumina heme WGS interpretation solution.
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