Distinct molecular profile of IRF4-rearranged large B-cell lymphoma
Por:
Ramis-Zaldivar, JE, Gonzalez-Farre, B, Balague, O, Celis, V, Nadeu, F, Salmeron-Villalobos, J, Andres, M, Martin-Guerrero, I, Garrido-Pontnou, M, Gaafar, A, Sunol, M, Barcena, C, Garcia-Bragado, F, Andion, M, Azorin, D, Astigarraga, I, de Ilurdoz, MS, Sabado, C, Gallego, S, Verdu-Amoros, J, Fernandez-Delgado, R, Perez, V, Tapia, G, Mozos, A, Torrent, M, Solano-Paez, P, Rivas-Delgado, A, Dlouhy, I, Clot, G, Enjuanes, A, Lopez-Guillermo, A, Galera, P, Oberley, MJ, Maguire, A, Ramsower, C, Rimsza, LM, Quintanilla-Martinez, L, Jaffe, ES, Campo, E, Salaverria, I
Publicada:
23 ene 2020
Resumen:
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 pound years using an integrated approach, including targeted gene sequencing, copynumber arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-kB 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.
Filiaciones:
Ramis-Zaldivar, JE:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Gonzalez-Farre, B:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Balague, O:
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Celis, V:
Hosp St Joan de Deu, Pediat Oncol Dept, Esplugas de Llobregat, Spain
Nadeu, F:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Salmeron-Villalobos, J:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Andres, M:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia, Spain
Martin-Guerrero, I:
Univ Basque Country, Univ Pais Vasco, Fac Sci & Technol, Dept Genet Phys Anthropol & Anim Physiol, Leioa, Spain
Hosp Univ Cruces Osakidetza, Biocruces Bizkaia Hlth Res Inst, Pediat Oncol Unit, Baracaldo, Spain
Garrido-Pontnou, M:
Hosp Univ Vall dHebron, Pathol Dept, Barcelona, Spain
Gaafar, A:
Hosp Univ Cruces Osakidetza, Biocruces Bizkaia Hlth Res Inst, Pathol Dept, Baracaldo, Spain
Sunol, M:
Hosp St Joan de Deu, Pathol Dept, Esplugas de Llobregat, Spain
Barcena, C:
Hosp Univ 12 Octubre, Pathol Dept, Madrid, Spain
Garcia-Bragado, F:
Complejo Hosp Navarra, Pathol Dept, Pamplona, Spain
Andion, M:
Hosp Univ Infant Nino Jesus, Pediat Oncol Dept, Madrid, Spain
Azorin, D:
Hosp Univ Infant Nino Jesus, Pathol Dept, Madrid, Spain
Astigarraga, I:
Hosp Univ Cruces Osakidetza, Biocruces Bizkaia Hlth Res Inst, Pediat Oncol Unit, Baracaldo, Spain
de Ilurdoz, MS:
Complejo Hosp Navarra, Pediat Oncol Dept, Pamplona, Spain
Sabado, C:
Hosp Univ Vall dHebron, Pediat Oncol Dept, Barcelona, Spain
Gallego, S:
Hosp Univ Vall dHebron, Pediat Oncol Dept, Barcelona, Spain
Verdu-Amoros, J:
Hosp Clin Univ Valencia, Pediat Oncol Dept, Valencia, Spain
Fernandez-Delgado, R:
Hosp Clin Univ Valencia, Pediat Oncol Dept, Valencia, Spain
Perez, V:
Hosp Univ 12 Octubre, Pediat Oncol Dept, Madrid, Spain
Tapia, G:
Hosp Trias & Pujol, Pathol Dept, Badalona, Spain
Mozos, A:
Hosp St Pau & Santa Creu, Pathol Dept, Barcelona, Spain
Torrent, M:
Hosp St Pau & Santa Creu, Pediat Oncol Dept, Barcelona, Spain
Solano-Paez, P:
Hosp Virgen Rocio, Pediat Oncol Dept, Seville, Spain
Rivas-Delgado, A:
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Dlouhy, I:
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Clot, G:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Enjuanes, A:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Lopez-Guillermo, A:
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Galera, P:
NIH, Lab Pathol, Bldg 10, Bethesda, MD 20892 USA
Oberley, MJ:
Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA
Maguire, A:
Mayo Clin, Dept Res, Scottsdale, AZ USA
Ramsower, C:
Mayo Clin, Dept Res, Scottsdale, AZ USA
Rimsza, LM:
Mayo Clin, Dept Lab Med & Pathol, Phoenix, AZ USA
Quintanilla-Martinez, L:
Eberhard Karls Univ Tubingen, Univ Hosp Tubingen, Inst Pathol, Tubingen, Germany
Jaffe, ES:
NIH, Lab Pathol, Bldg 10, Bethesda, MD 20892 USA
Campo, E:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Univ Barcelona, Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
Salaverria, I:
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Green Published, Bronze
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