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

Jie He, Omar Abdel-Wahab, Michelle K. Nahas, Kai Wang, Raajit K. Rampal, Andrew M. Intlekofer, Jay Patel, Andrei Krivstov, Garrett M. Frampton, Lauren E. Young, Shan Zhong, Mark Bailey, Jared R. White, Steven Roels, Jason Deffenbaugh, Alex Fichtenholtz, Timothy Brennan, Mark Rosenzweig, Kimberly Pelak, Kristina M. Knapp, Kristina W. Brennan, Amy L. Donahue, Geneva Young, Lazaro Garcia, Selmira T. Beckstrom, Mandy Zhao, Emily White, Vera Banning, Jamie Buell, Kiel Iwanik, Jeffrey S. Ross, Deborah Morosini, Anas Younes, Alan M. Hanash, Elisabeth Paietta, Kathryn Roberts, Charles Mullighan, Ahmet Dogan, Scott A. Armstrong, Tariq Mughal, Jo-Anne Vergilio, Elaine Labrecque, Rachel Erlich, Christine Vietz, Roman Yelensky, Philip J. Stephens, Vincent A. Miller, Marcel R. M. van den Brink, Geoff A. Otto, Doron Lipson and Ross L. Levine

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.