The majority of the tests being ordered are not helpful for lymphoblastic leukemia. FoundationOne Heme is a comprehensive genomic profiling (CGP) test combining DNA and RNA sequencing for patients with hematologic malignancies, sarcomas or solid tumors where RNA sequencing is desired. FoundationOne Heme detects known, novel, and complex fusion events as well as other common genomic alterations (substitutions, indels, and CNVs). This laboratory-developed test (LDT) can be used by physicians to identify potential targeted therapy options, detect alterations in prognostic genes, and sub-classify sarcoma diagnoses.
n the validation study, MSKCC researchers who developed the new Heme test in collaboration with Foundation Medicine put it through its paces by comparing results from the newer assay with those of Foundation’s original DNA-only FoundationOne test in order to assess its analytic accuracy in detecting substitutions, insertions and deletions, and copy number alterations.

In the validation study, the MSKCC investigators first reanalyzed 47 samples that were previously profiled with FoundationOne, in which 169 alterations were initially identified in 55 genes common to both assays. Comparing results of the Heme test against the original FoundationOne results, the concordance between the two was 99.4 percent, the authors wrote.

The group also performed an experiment using pooled cell lines with known genomic rearrangements to create mixtures representing a range of clinically relevant tumor fractions, and compared the genomic rearrangements detected in the pooled samples relative to the initial constituent cell lines.

According to the authors, FoundationOne Heme’s sensitivity for fusion detection at 20 to 100 percent tumor fraction was 100 percent, and it remained 98 percent sensitive even down to a 10 percent tumor fraction. There were also only a few false-positive calls, yielding a positive predictive value of more than 98 percent.

In addition to this comparison, the MSKCC researchers performed blinded comparisons with CLIA-certified diagnostic assays, including a Sequenom assay, RT-PCR, FISH, and PCR fragment analysis for 76 clinical specimens.

These specimens had been previously tested for 214 clinically relevant alterations in 11 genes that are known and routinely tested in clinical practice in hematologic cancers including AML, ALL, and MDS. In this comparison the overall concordance between FoundationOne Heme and these other assays was 99 percent.

More specifically, of 101 genomic alterations identified by the Sequenom assay or by PCR fragment analysis, 100 were also called by FoundationOne Heme.

Meanwhile, amongst the negative genomic alterations reported previously using the other assays, FoundationOne Heme confirmed 111 negative calls and identified two additional IDH2 R140Q mutations that were not detected by the reference methods. These two IDH2 alterations were later confirmed in an independent validation using the Ion Torrent AmpliSeq platform.

In addition to the concordance analysis, genomic profiling of the 76 test samples using FoundationOne Heme also identified 126 additional somatic alterations including clinically relevant genomic alterations in KRAS, TET2, EZH2, and DNMT3A.

To my knowledge, beyond validation, there are no confirming study of this test’s performance and no guidelines that recommend it.