Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials
| Autor: | Lisa Kim, Pablo Tamayo, Vincent A. Miller, Catriona Jamieson, Razelle Kurzrock, Matthew J. Wieduwilt, Aaron M. Goodman, Tariq I. Mughal, Jo-Anne Vergilio, Michael Y. Choi, Natalie Galanina, Huwate Yeerna, Carolyn Mulroney, Rafael Bejar |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Genomic profiling Lymphoma Pediatric Cancer Chronic lymphocytic leukemia precision medicine Oncology and Carcinogenesis myeloid malignancies lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Rare Diseases Internal medicine hemic and lymphatic diseases Genetics Medicine Multiple myeloma Myeloproliferative neoplasm Cancer Pediatric next generation sequencing business.industry Human Genome Myeloid leukemia Hematology Precision medicine medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Clinical trial lymphoid malignancies 030104 developmental biology 030220 oncology & carcinogenesis business Biotechnology |
| Zdroj: | Cancers, Vol 11, Iss 1, p 11 (2018) Cancers Cancers, vol 11, iss 1 Volume 11 Issue 1 |
| ISSN: | 2072-6694 |
| Popis: | 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 &ge 1 genomic alteration(s) 170/227 (75%), &ge 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. |
| Databáze: | OpenAIRE |
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