Foundation Medicine and Memorial Sloan Kettering Publish Validation Data for FoundationOne® Heme in the Journal Blood
New Data Demonstrate Accuracy and Clinical Application of
Comprehensive Genomic Profiling to Improve the Diagnosis and Treatment
"Foundation Medicine has an established track record of developing
genomic profiling assays with the highest standards of analytical and
clinical validation," said
"The development of FoundationOne Heme represents a state-of-the-art
genomics assay which can be used to profile patients with hematologic
malignancies worldwide, which is a critical step in improving outcomes
for all patients," stated
Conventional diagnostic assays, including FISH and real-time PCR, are designed to identify a sub-set of genomic alterations, and in some cases, there are no assays that can reliably identify specific rearrangements. FoundationOne Heme, an integrated DNA/RNA platform using targeted hybrid-capture next-generation sequencing, is a proven and effective comprehensive genomic profile developed to detect all types of genomic alterations with therapeutic relevance, including single-nucleotide substitutions, insertions and deletions, copy number alterations and rearrangements, which are not fully evaluated using conventional diagnostic assays.
Key Study Findings
Established analytic accuracy of detecting substitutions, insertions
and deletions (indels) and copy number alterations (CNAs) by comparing
the performance of the new assay with Foundation Medicine's DNA-only
assay that has previously undergone comprehensive validation across a
large number of clinical samples. Compared to FoundationOne,
FoundationOne Heme contains an additional 90 genes relevant to
- Samples that were previously profiled with a validated test in which 169 alterations were identified in 55 genes common to both assays. The concordance between the two sets of results was 99.4%.
Blinded comparisons were performed with CLIA-certified diagnostic
assays, including Sequenom, RT-PCR, FISH and PCR fragment analysis,
for 76 clinical specimens previously tested for 214 clinical relevant
alterations in 11 genes that are known and routinely tested in
clinical practice in AML, ALL and MDS.
- Overall concordance was 99% (211/214).
- In addition to the concordance analysis, genomic profiling of the 76 test samples identified 126 additional somatic alterations which are not covered by available hot spot assays in the given disease type, including clinically relevant genomic alterations in KRAS, TET2, EZH2, and DNMT3A.
- In independent low frequency variants ( < 10% mutant allele frequency), 20 of 21 variants were confirmed from AmpliSeq assay and another hotspot clinical assay.
Combined DNA and RNA sequencing approach accurately detects a wide
variety of genomic rearrangements and gene fusions with immediate
clinical value in hematologic malignancies.
- Sensitivity for fusion detection at 20% or greater tumor fraction was 100% (161/161) and 98% (84/86) at 10% tumor fraction.
Clinical experiences from 3,696 hematologic malignancies are
summarized, with a high fraction of clinically relevant genomic
- At least one driver alteration was identified in 95% tumor specimens, and 77% cases harbored at least one alteration linked to a commercially available targeted therapy or one that is in clinical development. In addition, 61% of cases harbored at least one alteration with known prognostic relevance in that tumor type.
- Genomic rearrangements were detected from 37% of clinical hematologic malignancies; known and novel fusions in kinase drug targets are highlighted.
- In 16 cases of high-risk, BCR-ABL-negative B-ALL malignancies, known and novel clinical relevant genomic alterations were detected by FoundationOne Heme, and gene fusions involving JAK2, CRLF2 and EPOR were detected in 9 of 16 cases.
About Memorial Sloan Kettering
We are the world's oldest and largest private cancer center, home to more than 14,000 physicians, scientists, nurses, and staff united by a relentless dedication to conquering cancer. As an independent institution, we combine 130 years of research and clinical leadership with the freedom to provide highly individualized, exceptional care to each patient. And our always-evolving educational programs continue to train new leaders in the field, here and around the world. For more information, go to www.mskcc.org.
Cautionary Note Regarding Forward-Looking Statements for
This press release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, statements regarding the performance of
FoundationOne Heme; the ability of comprehensive genomic profiling,
including FoundationOne Heme, to match patients with therapeutic
treatments; and the integration of FoundationOne Heme into clinical
practice. All such forward-looking statements are based on
management's current expectations of future events and are subject to a
number of risks and uncertainties that could cause actual results to
differ materially and adversely from those set forth in or implied by
such forward-looking statements. These risks and uncertainties
include the risks that FoundationOne Heme does not perform in the same
manner as the published data and the risks described under the caption
"Risk Factors" in
For Memorial Sloan Kettering
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