Portal de Periódicos da CAPES

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

2016; Elsevier BV; Volume: 127; Issue: 24 Linguagem: Inglês

10.1182/blood-2015-08-664649

1528-0020

Jie He, Omar Abdel‐Wahab, Michelle Nahas, Kai Wang, Raajit K. Rampal, Andrew M. Intlekofer, Jay Patel, Andrei V Krivstov, Garrett M. Frampton, Lauren Young, Shan Zhong, Mark Bailey, Jared White, Steven Roels, Jason Deffenbaugh, Alex Fichtenholtz, Timothy A Brennan, Mark R. Rosenzweig, Kimberly Pelak, Kristina M. Knapp, Kristina Brennan, Amy Donahue, Geneva Young, Lázaro Ibrahim Romero García, 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 G. Roberts, Charles G. Mullighan, Ahmet Doğan, Scott A. Armstrong, Tariq I. 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 Otto, Doron Lipson, Ross L. Levine,

Viral-associated cancers and disorders

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 blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-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 that 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.