Targetable genetic features of primary testicular and primary central nervous system lymphomas
| Autor: | Ekaterina S. Jordanova, Bjoern Chapuy, Chip Stewart, Azra H. Ligon, Liye Zhang, Andrew Dunford, Heather Homer, Gerald Illerhaus, Aaron R. Thorner, Ryan Abo, Miyuki Aono, Scott J. Rodig, Todd R. Golub, Keith L. Ligon, Yuxiang Tan, David Meredith, Margaret A. Shipp, Gad Getz, Stefano Monti, Heather Sun, Daphne de Jong, Gang Liu, Margaretha G.M. Roemer, Erica Linden, Judith A. Ferry, Geraldine S. Pinkus, Friedrich Feuerhake, Matthew D. Ducar, Paul Van Hummelen, Gordon J. Freeman, Daniel Gusenleitner |
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| Přispěvatelé: | Pathology, Obstetrics and gynaecology, CCA - Target Discovery & Preclinial Therapy Development, Other departments |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Immunology Biology medicine.disease_cause Mediastinal Neoplasms Biochemistry Translocation Genetic Targeted therapy Central Nervous System Neoplasms 03 medical and health sciences 0302 clinical medicine Testicular Neoplasms medicine Humans B-cell lymphoma Genetics Mutation Lymphoid Neoplasia Primary central nervous system lymphoma Cell Biology Hematology medicine.disease BCL6 Neoplasm Proteins Lymphoma 030104 developmental biology Testicular Lymphoma Genetic Loci 030220 oncology & carcinogenesis Female Lymphoma Large B-Cell Diffuse Diffuse large B-cell lymphoma |
| Zdroj: | Blood, 127(7), 869-881. American Society of Hematology Chapuy, B, Roemer, M G M, Stewart, C, Tan, Y, Abo, R P, Zhang, L, Dunford, A J, Meredith, D M, Thorner, A R, Jordanova, E S, Liu, G, Feuerhake, F, Ducar, M D, Illerhaus, G, Gusenleitner, D, Linden, E A, Sun, H H, Homer, H, Aono, M, Pinkus, G S, Ligon, A H, Ligon, K L, Ferry, J A, Freeman, G J, van Hummelen, P, Golub, T R, Getz, G, Rodig, S J, de Jong, D, Monti, S & Shipp, M A 2016, ' Targetable genetic features of primary testicular and primary central nervous system lymphomas ', Blood, vol. 127, no. 7, pp. 869-881 . https://doi.org/10.1182/blood-2015-10-673236 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. |
| Databáze: | OpenAIRE |
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