Posts Tagged ‘hematologic malignancies’

Validation of FoundationOne Heme in New Study: Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

Reporter: Aviva Lev-Ari, PhD, RN


Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

  1. Jie He1,
  2. Omar Abdel-Wahab2,
  3. Michelle K. Nahas1,
  4. Kai Wang1,
  5. Raajit K. Rampal3,
  6. Andrew M. Intlekofer4,
  7. Jay Patel3,
  8. Andrei Krivstov5,
  9. Garrett M. Frampton1,
  10. Lauren E. Young1,
  11. Shan Zhong1,
  12. Mark Bailey1,
  13. Jared R. White1,
  14. Steven Roels1,
  15. Jason Deffenbaugh1,
  16. Alex Fichtenholtz1,
  17. Timothy Brennan1,
  18. Mark Rosenzweig1,
  19. Kimberly Pelak1,
  20. Kristina M. Knapp5,
  21. Kristina W. Brennan1,
  22. Amy L. Donahue1,
  23. Geneva Young1,
  24. Lazaro Garcia1,
  25. Selmira T. Beckstrom1,
  26. Mandy Zhao1,
  27. Emily White1,
  28. Vera Banning1,
  29. Jamie Buell1,
  30. Kiel Iwanik1,
  31. Jeffrey S. Ross1,
  32. Deborah Morosini1,
  33. Anas Younes4,
  34. Alan M. Hanash6,
  35. Elisabeth Paietta7,
  36. Kathryn Roberts8,
  37. Charles Mullighan8,
  38. Ahmet Dogan9,
  39. Scott A. Armstrong5,
  40. Tariq Mughal1,
  41. Jo-Anne Vergilio1,
  42. Elaine Labrecque1,
  43. Rachel Erlich1,
  44. Christine Vietz1,
  45. Roman Yelensky1,
  46. Philip J. Stephens1,
  47. Vincent A. Miller1,
  48. Marcel R. M. van den Brink10,
  49. Geoff A. Otto1,
  50. Doron Lipson1, and
  51. Ross L. Levine2,*
Author Affiliations
  1. * Corresponding author; email: leviner@mskcc.org

Key Points

  • Novel clinically-available comprehensive genomic profiling of both DNA and RNA in hematologic malignancies.

  • Profiling of 3696 clinical hematologic tumors identified somatic alterations that impact diagnosis, prognosis, and therapeutic selection.


The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs) and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded (FFPE), blood and bone marrow samples with high accuracy in a clinically relevant timeframe, which is performed in our CLIA-certified CAP-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs and gene fusions, with similar accuracy to lower-throughput assays which focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically-relevant genomic alterations with therapeutic relevance.

  • Submitted August 16, 2015.
  • Accepted February 28, 2016.



Foundation Medicine Shares Results From Validation of FoundationOne Heme in New Study

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.

Importantly, the study also showed that the molecular information supplied by the test can help accurately match patients with a particular targeted therapy.

In the study Foundation Medicine shared clinical data from genomic profiling of 3,696 hematologic malignancies submitted to its CLIA-certified, NYS-approved lab.

More than 90 percent of the specimens — 3,433 out of 3696 — were successfully characterized. The test identified at least one driver alteration in 95 percent of the tumor specimens, and results showed that 77 percent of the cases harbored at least one alteration linked to a commercially available targeted therapy or one that is in clinical development, the MSKCC researchers reported.

In addition, 61 percent of the cases harbored at least one alteration with known prognostic relevance in that tumor type.

In discussion of the results, the study authors argued that clinical merit of the test was underscored by the demonstrated ability to identify genetic lesions with prognostic and therapeutic relevance in specific diseases.

For example, the authors wrote, “In the case of B-cell ALL … the challenge has been that the critical genes … can be altered by whole gene/intragenic deletions, DNA base-pair substitutions, and larger indels, as well as chromosomal, intergenic, and cryptic rearrangements, which lead to expression of fusion transcripts.”

“Currently, most centers use an amalgam of DNA, FISH, and gene-specific RNA approaches to identify a subset of the most critical genetic lesions in B-ALL. Our assay provides a single profiling platform that can reliably identify all known actionable disease alleles relevant to B-ALL to improve diagnosis and risk-adapted therapy for B-ALL patients,” they wrote.



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