Genomic landscape of follicular lymphoma across a wide spectrum of clinical behaviors.
copy number alteration
follicular lymphoma
genomics
next-generation sequencing
prognosis
survival
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
10
03
2023
received:
26
12
2022
accepted:
12
03
2023
medline:
23
10
2023
pubmed:
31
3
2023
entrez:
30
3
2023
Statut:
ppublish
Résumé
While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1-3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy-neutral loss of heterozygosity (CN-LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3-p13.2 CN-LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
631-643Subventions
Organisme : Fundación Asociación Española Contra el Cancer AECC/CIBERONC
ID : PROYE18020BEA
Organisme : Marató TV3-Cancer
ID : 201904-30
Organisme : Generalitat de Catalunya Suport Grups de Recerca AGAUR
ID : 2021-SGR-01293
Organisme : Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, "Cofinanciado por la Unión Europea" and Fondos FEDER: European Regional Development Fund "Una manera de hacer Europa"
ID : PI17/01061;PI19/00887;INT20/00050
Informations de copyright
© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
Références
Bachy E, Seymour JF, Feugier P, et al. Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study. J Clin Oncol. 2019;37(31):2815-2824. https://doi.org/10.1200/JCO.19.01073
Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol. 2019;184(5):753-759. https://doi.org/10.1111/bjh.15708
Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516-2522. https://doi.org/10.1200/JCO.2014.59.7534
Alonso-Álvarez S, Magnano L, Alcoceba M, et al. Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group. Br J Haematol. 2017;178(5):699-708. https://doi.org/10.1111/bjh.14831
Limpens J, Stad R, Vos C, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85(9):2528-2536. https://doi.org/10.1182/blood.v85.9.2528.bloodjournal8592528
Kridel R, Chan FC, Mottok A, et al. Histological transformation and progression in follicular lymphoma: a clonal evolution study. PLoS Med. 2016;13(12):1-25. https://doi.org/10.1371/journal.pmed.1002197
Okosun J, Bödör C, Wang J, et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2014;46(2):176-181. https://doi.org/10.1038/ng.2856
Pasqualucci L, Khiabanian H, Fangazio M, et al. Genetics of follicular lymphoma transformation. Cell Rep. 2014;6(1):130-140. https://doi.org/10.1016/j.celrep.2013.12.027
Green MR, Kihira S, Liu CL, et al. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc Natl Acad Sci U S A. 2015;112(10):E1116-E1125. https://doi.org/10.1073/pnas.1501199112
Pasqualucci L, Dominguez-Sola D, Chiarenza A, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189-196. https://doi.org/10.1038/nature09730
Morin RD, Johnson NA, Severson TM, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42(2):181-185. https://doi.org/10.1038/ng.518
Bouska A, McKeithan TW, Deffenbacher KE, et al. Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma. Blood. 2014;123(11):1681-1690. https://doi.org/10.1182/blood-2013-05-500595
Cheung KJJ, Shah SP, Steidl C, et al. Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood. 2009;113(1):137-148. https://doi.org/10.1182/blood-2008-02-140616
Johnson NA, Al-Tourah A, Brown CJ, Connors JM, Gascoyne RD, Horsman DE. Prognostic significance of secondary cytogenetic alterations in follicular lymphomas. Genes Chromosom Cancer. 2008;47(12):1038-1048. https://doi.org/10.1002/gcc.20606
Mozas P, Rivero A, López-Guillermo A. Past, present and future of prognostic scores in follicular lymphoma. Blood Rev. 2021;50:100865. https://doi.org/10.1016/j.blre.2021.100865
Pastore A, Jurinovic V, Kridel R, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16(9):1111-1122. https://doi.org/10.1016/S1470-2045(15)00169-2
Qu X, Li H, Braziel RM, et al. Genomic alterations important for the prognosis in patients with follicular lymphoma treated in SWOG study S0016. Blood. 2019;133(1):81-93. https://doi.org/10.1182/blood-2018-07-865428
Jurinovic V, Kridel R, Staiger AM, et al. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy. Blood. 2016;128(8):1112-1120. https://doi.org/10.1182/blood-2016-05-717355
Huet S, Tesson B, Jais JP, et al. A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts. Lancet Oncol. 2018;19(4):549-561. https://doi.org/10.1016/S1470-2045(18)30102-5
Brice P, Bastion Y, Lepage E, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d’Etude des Lymphomes Folliculaires. J Clin Oncol. 1997;15(3):1110-1117. https://doi.org/10.1200/JCO.1997.15.3.1110
Hudson TJ, Anderson W, Aretz A, et al. International network of cancer genome projects. Nature. 2010;464(7291):993-998. https://doi.org/10.1038/nature08987
Bell D, Gaillard F, IARC. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4t; 2010. https://doi.org/10.53347/rid-9250
Nadeu F, Delgado J, Royo C, et al. Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia. Blood. 2016;127(17):2122-2130. https://doi.org/10.1182/blood-2015-07-659144
Rivas-Delgado A, Nadeu F, Enjuanes A, et al. Mutational landscape and tumor burden assessed by cell-free DNA in diffuse large B-cell lymphoma in a population-based study. Clin Cancer Res. 2021;27(2):513-521. https://doi.org/10.1158/1078-0432.CCR-20-2558
Shuai S, Suzuki H, Diaz-Navarro A, et al. The U1 spliceosomal RNA is recurrently mutated in multiple cancers. Nature. 2019;574(7780):712-716. https://doi.org/10.1038/s41586-019-1651-z
Betts MJ, Lu Q, Jiang Y, et al. Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions. Nucleic Acids Res. 2015;43(2):e10. https://doi.org/10.1093/nar/gku1094
Green MR. Chromatin modifying gene mutations in follicular lymphoma. Blood. 2018;131(6):595-604. https://doi.org/10.1182/blood-2017-08-737361
Baliñas-Gavira C, Rodríguez MI, Andrades A, et al. Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia. 2020;34(10):2722-2735. https://doi.org/10.1038/s41375-020-0919-5
Yildiz M, Li H, Bernard D, et al. Lymphoid neoplasia: activating stat6 mutations in follicular lymphoma. Blood. 2015;125(4):668-679. https://doi.org/10.1182/blood-2014-06-582650
Krysiak K, Gomez F, White BS, et al. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017;129(4):473-483. https://doi.org/10.1182/blood-2016-07-729954
Okosun J, Wolfson RL, Wang J, et al. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nat Genet. 2016;48(2):183-188. https://doi.org/10.1038/ng.3473
Lenz G, Davis RE, Ngo VN, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science (80- ). 2008;319(5870):1676-1679. https://doi.org/10.1126/science.1153629
Che T, You Y, Wang D, Tanner MJ, Dixit VM, Lin X. MALT1/Paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-κB activation. J Biol Chem. 2004;279(16):15870-15876. https://doi.org/10.1074/jbc.M310599200
Saijo K, Schmedt C, Suhsin I, et al. Essential role of Src-family protein tyrosine kinases in NF-κB activation during B cell development. Nat Immunol. 2003;4(3):274-279. https://doi.org/10.1038/ni893
Gresset A, Sondek J, Harden TK. The phospholipase C isozymes and their regulation. Subcell Biochem. 2015;58:61-94. https://doi.org/10.1007/978-94-007-3012-0_3
Mary Photini S, Chaiwangyen W, Weber M, et al. PIM kinases 1, 2 and 3 in intracellular LIF signaling, proliferation and apoptosis in trophoblastic cells. Exp Cell Res. 2017;359(1):275-283. https://doi.org/10.1016/j.yexcr.2017.07.019
Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006;21(6):749-760. https://doi.org/10.1016/j.molcel.2006.02.009
Kong HJ, Anderson DE, Lee CH, et al. Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J Immunol. 2007;179(1):26-30. https://doi.org/10.4049/jimmunol.179.1.26
Trabuco LG, Lise S, Petsalaki E, Russell RB. PepSite: prediction of peptide-binding sites from protein surfaces. Nucleic Acids Res. 2012;40(W1):W423-W427. https://doi.org/10.1093/nar/gks398
Forbes SA, Beare D, Boutselakis H, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017;45(D1):D777-D783. https://doi.org/10.1093/nar/gkw1121
Kumar E, Pickard L, Okosun J. Pathogenesis of follicular lymphoma: genetics to the microenvironment to clinical translation. Br J Haematol. 2021;194(5):1-12. https://doi.org/10.1111/bjh.17383
Cheung KJJ, Delaney A, Ben-Neriah S, et al. High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy-neutral loss of heterozygosity and copy number alterations that target single genes. Genes Chromosom Cancer. 2010;49(8):669-681. https://doi.org/10.1002/gcc.20780
Huet S, Szafer-Glusman E, Xerri L, et al. Evaluation of clinicogenetic risk models for outcome of follicular lymphoma patients in the prima trial. Hematol Oncol. 2017;35:96-97. https://doi.org/10.1002/hon.2437_85
Crouch S, Painter D, Barrans SL, et al. Molecular subclusters of follicular lymphoma: a report from the UK’s Haematological Malignancy Research Network. Blood Adv. 2022;6(21):5716-5731. https://doi.org/10.1182/bloodadvances.2021005284
Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679-690. https://doi.org/10.1038/s41591-018-0016-8
Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396-1407. https://doi.org/10.1056/nejmoa1801445
Leich E, Salaverria I, Bea S, et al. Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood. 2009;114(4):826-834. https://doi.org/10.1182/blood-2009-01-198580
Horn H, Schmelter C, Leich E, et al. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica. 2011;96(9):1327-1334. https://doi.org/10.3324/haematol.2011.042531
Pindzola GM, Razzaghi R, Tavory RN, et al. Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma. Blood. 2022;140(10):1119-1131. https://doi.org/10.1182/blood.2022015926
Hsi ED, Jung SH, Lai R, et al. Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study. Leuk Lymphoma. 2008;49(11):2081-2090. https://doi.org/10.1080/10428190802419640
Ennishi D, Healy S, Bashashati A, et al. TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma. Nat Med. 2020;26(4):577-588. https://doi.org/10.1038/s41591-020-0757-z
Pickard L, Palladino G, Okosun J. Follicular lymphoma genomics. Leuk Lymphoma. 2020;61(10):2313-2323. https://doi.org/10.1080/10428194.2020.1762883
Alhejaily A, Day AG, Feilotter HE, Baetz T, LeBrun DP. Inactivation of the CDKN2A tumor-suppressor gene by deletion or methylation is common at diagnosis in follicular lymphoma and associated with poor clinical outcome. Clin Cancer Res. 2014;20(6):1676-1686. https://doi.org/10.1158/1078-0432.CCR-13-2175
Jiménez-Ubieto A, Poza M, Martin-Muñoz A, et al. Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT. Leukemia. 2023;37(3):659-669. https://doi.org/10.1038/s41375-022-01803-x
Morin RD, Mendez-Lago M, Mungall AJ, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298-303. https://doi.org/10.1038/nature10351
Davis RE, Ngo VN, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277):88-92. https://doi.org/10.1038/nature08638
Bohers E, Mareschal S, Bouzelfen A, et al. Targetable activating mutations are very frequent in GCB and ABC diffuse large B-cell lymphoma. Genes Chromosom Cancer. 2014;53(2):144-153. https://doi.org/10.1002/gcc.22126
Oke V, Wahren-Herlenius M. The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review. J Autoimmun. 2012;39(1-2):77-82. https://doi.org/10.1016/j.jaut.2012.01.014
Furman RR, Cheng S, Lu P, et al. Ibrutinib resistance in chronic lymphocytic leukemia. N Engl J Med. 2014;370(24):2352-2354. https://doi.org/10.1056/nejmc1402716
Kuo HP, Ezell SA, Hsieh S, et al. The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma. Am J Cancer Res. 2016;6(11):2489-2501. https://doi.org/10.1182/blood.v126.23.699.699
Wang J, Anderson PD, Luo W, Gius D, Roh M, Abdulkadir SA. Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells. Oncogene. 2012;31(14):1794-1803. https://doi.org/10.1038/onc.2011.371