%0 Journal Article
%T Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials
%A Aaron Goodman
%A Carolyn Mulroney
%A Catriona Jamieson
%A Huwate Yeerna
%A Jo-Anne Vergilio
%A Lisa Kim
%A Matthew Wieduwilt
%A Michael Choi
%A Natalie Galanina
%A Pablo Tamayo
%A Rafael Bejar
%A Razelle Kurzrock
%A Tariq I. Mughal
%A Vincent Miller
%J Archive of "Cancers".
%D 2019
%R 10.3390/cancers11010011
%X 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 ¡Ý1 genomic alteration(s); 170/227 (75%), ¡Ý1 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
%K next generation sequencing
%K lymphoid malignancies
%K myeloid malignancies
%K precision medicine
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356731/