{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:04:21Z","timestamp":1778864661225,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA023100"],"award-info":[{"award-number":["P30 CA023100"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u22651 genomic alteration(s); 170\/227 (75%), \u22651 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.<\/jats:p>","DOI":"10.3390\/cancers11010011","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T12:14:49Z","timestamp":1545394489000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-3260","authenticated-orcid":false,"given":"Natalie","family":"Galanina","sequence":"first","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Bejar","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Choi","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Goodman","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Wieduwilt","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Mulroney","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Kim","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huwate","family":"Yeerna","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Statistical Physics, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9360-4668","authenticated-orcid":false,"given":"Pablo","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Statistical Physics, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo-Anne","family":"Vergilio","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc., Cambridge, MA 02141, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq I.","family":"Mughal","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc., Cambridge, MA 02141, USA"},{"name":"Tufts University Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Miller","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc., Cambridge, MA 02141, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriona","family":"Jamieson","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1158\/0008-5472.CAN-14-2329","article-title":"Unique molecular landscapes in cancer: Implications for individualized, curated drug combinations","volume":"74","author":"Wheler","year":"2014","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1158\/1535-7163.MCT-15-0795","article-title":"Precision Oncology: The UC San Diego Moores Cancer Center PREDICT 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