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Open AccessFeature PaperArticle

Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials

1
Department of Medicine, Division of Hematology/Oncology and Center for Personalized Cancer Therapy, University of California San Diego, 3855 Health Science Drive #0987, La Jolla, CA 92093, USA
2
Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA 92093, USA
3
Department of Medicine, Division of Statistical Physics, University of California San Diego, La Jolla, CA 92093, USA
4
Foundation Medicine Inc., Cambridge, MA 02141, USA
5
Tufts University Medical Center, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(1), 11; https://doi.org/10.3390/cancers11010011
Received: 19 November 2018 / Revised: 11 December 2018 / Accepted: 11 December 2018 / Published: 21 December 2018
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability. Results: Overall, 227 patients (96.5%) had adequate tissue. Most common diagnoses included myelodysplastic syndrome (22.9%), chronic lymphocytic leukemia (17.2%), non-Hodgkin lymphoma (13.2%), acute myeloid leukemia (11%), myeloproliferative neoplasm (9.2%), acute lymphoblastic leukemia (8.8%), and multiple myeloma (7.5%). Most patients (N = 197/227 (87%)) harbored ≥1 genomic alteration(s); 170/227 (75%), ≥1 potentially actionable alteration(s) targetable by an FDA-approved (mostly off-label) or an investigational agent. Altogether, 546 distinct alterations were seen, most commonly involving TP53 (10.8%), TET2 (4.6%), and DNMT3A (4.2%). The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB (higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents. View Full-Text
Keywords: next generation sequencing; lymphoid malignancies; myeloid malignancies; precision medicine next generation sequencing; lymphoid malignancies; myeloid malignancies; precision medicine
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Galanina, N.; Bejar, R.; Choi, M.; Goodman, A.; Wieduwilt, M.; Mulroney, C.; Kim, L.; Yeerna, H.; Tamayo, P.; Vergilio, J.-A.; Mughal, T.I.; Miller, V.; Jamieson, C.; Kurzrock, R. Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials. Cancers 2019, 11, 11.

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