Distinct molecular profile of IRF4-rearranged large B-cell lymphoma
| Autor: | Colleen Ramsower, Matthew J. Oberley, Julia Salmeron-Villalobos, Marta Garrido-Pontnou, Ayman Gaafar, Constantino Sábado, Montserrat Torrent, Leticia Quintanilla-Martinez, Alfredo Rivas-Delgado, Mara Andrés, Federico Garcia-Bragado, Elaine S. Jaffe, Lisa M. Rimsza, Mariona Suñol, Elias Campo, Anna Mozos, Rafael Fernandez-Delgado, Alanna Maguire, Itziar Salaverria, Carmen Bárcena, Itziar Astigarraga, Blanca Gonzalez-Farre, Olga Balagué, Ivan Dlouhy, Armando López-Guillermo, Maitane Andión, Idoia Martin-Guerrero, Ferran Nadeu, Joan Enric Ramis-Zaldivar, Anna Enjuanes, Pallavi Galera, Palma Solano-Páez, Jaime Verdu-Amoros, Guillem Clot, Soledad Gallego, Veronica Celis, Vanesa Perez, Maria Sagaseta de Ilurdoz, Gustavo Tapia, Daniel Azorín |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Adolescent Immunology Gene mutation Biology Biochemistry Young Adult CDKN2A medicine Humans Child B-cell lymphoma Chromosome 7 (human) Lymphoid Neoplasia Cell Biology Hematology CD79B Prognosis medicine.disease Lymphoma Gene expression profiling Child Preschool Interferon Regulatory Factors Mutation Cancer research Female Lymphoma Large B-Cell Diffuse Transcriptome Diffuse large B-cell lymphoma |
| Zdroj: | Blood r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu r-IGTP: Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Institut de Recerca Germans Trias i Pujol (IGTP) r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Universidad de Alicante (UA) BLOOD r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma–related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification. |
| Databáze: | OpenAIRE |
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