Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
16
06
2023
accepted:
02
08
2023
revised:
18
07
2023
medline:
4
10
2023
pubmed:
11
8
2023
entrez:
10
8
2023
Statut:
ppublish
Résumé
Knowledge on the pathogenesis of FL is mainly based on data derived from advanced/systemic stages of FL (sFL) and only small cohorts of localized FL (lFL) have been characterized intensively so far. Comprehensive analysis with profiling of somatic copy number alterations (SCNA) and whole exome sequencing (WES) was performed in 147 lFL and 122 sFL. Putative targets were analyzed for gene and protein expression. Overall, lFL and sFL, as well as BCL2 translocation-positive (BCL2+) and -negative (BCL2-) FL showed overlapping features in SCNA and mutational profiles. Significant differences between lFL and sFL, however, were detected for SCNA frequencies, e.g., in 18q-gains (14% lFL vs. 36% sFL; p = 0.0003). Although rare in lFL, gains in 18q21 were associated with inferior progression-free survival (PFS). The mutational landscape of lFL and sFL included typical genetic lesions. However, ARID1A mutations were significantly more often detected in sFL (29%) compared to lFL (6%, p = 0.0001). In BCL2 + FL mutations in KMT2D, BCL2, ABL2, IGLL5 and ARID1A were enriched, while STAT6 mutations more frequently occurred in BCL2- FL. Although the landscape of lFL and sFL showed overlapping features, molecular profiling revealed novel insights and identified gains in 18q21 as prognostic marker in lFL.
Identifiants
pubmed: 37563306
doi: 10.1038/s41375-023-01995-w
pii: 10.1038/s41375-023-01995-w
pmc: PMC10539171
doi:
Substances chimiques
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2058-2065Informations de copyright
© 2023. The Author(s).
Références
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues, 4th ed. Lyon: International Agency for Research on Cancer; 2017.
Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. Cancer J Clin. 2016;66:443–59.
doi: 10.3322/caac.21357
Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL, et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood. 2013;121:1604–11.
pubmed: 23297126
pmcid: 3587323
doi: 10.1182/blood-2012-09-457283
Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, 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;16:1111–22.
pubmed: 26256760
doi: 10.1016/S1470-2045(15)00169-2
Dreyling M, Ghielmini M, Rule S, Salles G, Ladetto M, Tonino SH, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32:298–308.
pubmed: 33249059
doi: 10.1016/j.annonc.2020.11.008
Batlevi CL, Sha F, Alperovich A, Ni A, Smith K, Ying Z, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10:74.
pubmed: 32678074
pmcid: 7366724
doi: 10.1038/s41408-020-00340-z
Leich E, Hoster E, Wartenberg M, Unterhalt M, Siebert R, Koch K, et al. Similar clinical features in follicular lymphomas with and without breaks in the BCL2 locus. Leukemia. 2016;30:854–60.
pubmed: 26621338
doi: 10.1038/leu.2015.330
Horn H, Jurinovic V, Leich E, Kalmbach S, Bausinger J, Staiger AM, et al. Molecular cytogenetic profiling reveals similarities and differences between localized nodal and systemic follicular lymphomas. HemaSphere. 2022;6:e767.
pubmed: 35974958
pmcid: 9371558
doi: 10.1097/HS9.0000000000000767
Staiger AM, Hoster E, Jurinovic V, Winter S, Leich E, Kalla C, et al. Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles. Blood. 2020;135:181–90.
pubmed: 31697802
doi: 10.1182/blood.2019000560
Leich E, Maier C, Bomben R, Vit F, Bosi A, Horn H, et al. Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage. Blood Adv. 2021;5:4890–4900.
pubmed: 34614504
pmcid: 9153045
doi: 10.1182/bloodadvances.2021005081
Herfarth K, Borchmann P, Schnaidt S, Hohloch K, Budach V, Engelhard M, et al. Rituximab with involved field irradiation for early-stage nodal follicular lymphoma: results of the MIR study. HemaSphere. 2018;2:e160.
pubmed: 31723798
pmcid: 6745956
doi: 10.1097/HS9.0000000000000160
Engelhard M, Unterhalt M, Hansmann ML, Stuschke M. Follicular lymphoma: curability by radiotherapy in limited stage nodal disease? Updated results of a randomized trial. Ann Oncol. 2011;22(Supplement 4):iv90–1.
Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725–32.
pubmed: 16123223
doi: 10.1182/blood-2005-01-0016
Frontzek F, Staiger AM, Zapukhlyak M, Xu W, Bonzheim I, Borgmann V, et al. Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma. Nat Commun. 2021;12:5183.
pubmed: 34465776
pmcid: 8408158
doi: 10.1038/s41467-021-25405-w
Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Küppers R, et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001;412:341–6.
pubmed: 11460166
doi: 10.1038/35085588
Cheung K-JJ, Shah SP, Steidl C, Johnson N, Relander T, Telenius A, et al. Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood. 2009;113:137–48.
pubmed: 18703704
doi: 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 Chromosomes Cancer. 2008;47:1038–48.
pubmed: 18720523
doi: 10.1002/gcc.20606
Viardot A, Möller P, Högel J, Werner K, Mechtersheimer G, Ho AD, et al. Clinicopathologic correlations of genomic gains and losses in follicular lymphoma. J Clin Oncol. 2002;20:4523–30.
pubmed: 12454108
doi: 10.1200/JCO.2002.12.006
Viardot AA, Barth TFE, Möller P, Döhner H, Bentz M. Cytogenetic evolution of follicular lymphoma. Semin Cancer Biol. 2003;13:183–90.
pubmed: 12959349
doi: 10.1016/S1044-579X(03)00014-2
Bernstein HB, Plasterer MC, Schiff SE, Kitchen CMR, Kitchen S, Zack JA. CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression and cell migration. J Immunol. 2006;177:3669–76.
pubmed: 16951326
doi: 10.4049/jimmunol.177.6.3669
Khurana D, Arneson LN, Schoon RA, Dick CJ, Leibson PJ. Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. J Immunol. 2007;178:3575–82.
pubmed: 17339454
doi: 10.4049/jimmunol.178.6.3575
Veillette A. NK cell regulation by SLAM family receptors and SAP-related adapters. Immunol Rev. 2006;214:22–34.
pubmed: 17100873
doi: 10.1111/j.1600-065X.2006.00453.x
Leich E, Salaverria I, Bea S, Zettl A, Wright G, Moreno V, et al. Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood. 2009;114:826–34.
pubmed: 19471018
pmcid: 2716022
doi: 10.1182/blood-2009-01-198580
Horsman DE, Okamoto I, Ludkovski O, Le N, Harder L, Gesk S, et al. Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes. Br J Haematol. 2003;120:424–33.
pubmed: 12580956
doi: 10.1046/j.1365-2141.2003.04086.x
Los-de Vries GT, Stevens WBC, van Dijk E, Langois-Jacques C, Clear AJ, Stathi P, et al. Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV. Blood Adv. 2022;6:5482–93.
pubmed: 35816682
pmcid: 9631713
doi: 10.1182/bloodadvances.2022008355
Wurster AL, Rodgers VL, White MF, Rothstein TL, Grusby MJ. Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL. J Biol Chem. 2002;277:27169–75.
pubmed: 12023955
doi: 10.1074/jbc.M201207200
Koch K, Hoster E, Unterhalt M, Ott G, Rosenwald A, Hansmann ML, et al. The composition of the microenvironment in follicular lymphoma is associated with the stage of the disease. Hum Pathol. 2012;43:2274–81.
pubmed: 22795355
doi: 10.1016/j.humpath.2012.03.025
Schmidt J, Salaverria I, Haake A, Bonzheim I, Adam P, Montes-Moreno S, et al. Increasing genomic and epigenomic complexity in the clonal evolution from in situ to manifest t(14;18)-positive follicular lymphoma. Leukemia. 2014;28:1103–12.
pubmed: 24153014
doi: 10.1038/leu.2013.307
Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA. 2007;104:20007–12.
pubmed: 18077431
pmcid: 2148413
doi: 10.1073/pnas.0710052104
Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R, Getz G. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011;12:R41.
pubmed: 21527027
pmcid: 3218867
doi: 10.1186/gb-2011-12-4-r41
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899–905.
pubmed: 20164920
pmcid: 2826709
doi: 10.1038/nature08822
Bignell GR, Greenman CD, Davies H, Butler AP, Edkins S, Andrews JM, et al. Signatures of mutation and selection in the cancer genome. Nature. 2010;463:893–8.
pubmed: 20164919
pmcid: 3145113
doi: 10.1038/nature08768
Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007;446:153–8.
pubmed: 17344846
pmcid: 2712719
doi: 10.1038/nature05610
Ochiai K, Yamaoka M, Swaminathan A, Shima H, Hiura H, Matsumoto M, et al. Chromatin protein PC4 orchestrates B cell differentiation by collaborating with IKAROS and IRF4. Cell Rep. 2020;33:108517.
pubmed: 33357426
doi: 10.1016/j.celrep.2020.108517
Tong KI, Yoon S, Isaev K, Bakhtiari M, Lackraj T, He MY, et al. Combined EZH2 Inhibition and IKAROS degradation leads to enhanced antitumor activity in diffuse large B-cell lymphoma. Clin Cancer Res. 2021;27:5401–14.
pubmed: 34168051
doi: 10.1158/1078-0432.CCR-20-4027
Nann D, Ramis-Zaldivar JE, Müller I, Gonzalez-Farre B, Schmidt J, Egan C, et al. Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease. Blood Adv. 2020;4:5652–65.
pubmed: 33211828
pmcid: 7686888
doi: 10.1182/bloodadvances.2020002944
Boyington JC, Sun PD. A structural perspective on MHC class I recognition by killer cell immunoglobulin-like receptors. Mol Immunol. 2002;38:1007–21.
pubmed: 11955593
doi: 10.1016/S0161-5890(02)00030-5
Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–51.
pubmed: 11861603
doi: 10.1146/annurev.immunol.20.092501.134942
Erbe AK, Wang W, Carmichael L, Hoefges A, Grzywacz B, Reville PK, et al. Follicular lymphoma patients with KIR2DL2 and KIR3DL1 and their ligands (HLA-C1 and HLA-Bw4) show improved outcome when receiving rituximab. J Immunother Cancer. 2019;7:70.
pubmed: 30871628
pmcid: 6419437
doi: 10.1186/s40425-019-0538-8
He L, Zhu H-Y, Qin S-C, Li Y, Miao Y, Liang J-H, et al. Low natural killer (NK) cell counts in peripheral blood adversely affect clinical outcome of patients with follicular lymphoma. Blood Cancer J. 2016;6:e457.
pubmed: 27518240
pmcid: 5022180
doi: 10.1038/bcj.2016.67
Cao S, Zhou DC, Oh C, Jayasinghe RG, Zhao Y, Yoon CJ, et al. Discovery of driver non-coding splice-site-creating mutations in cancer. Nat Commun. 2020;11:5573.
pubmed: 33149122
pmcid: 7642382
doi: 10.1038/s41467-020-19307-6
Dierlamm J, Murga Penas EM, Bentink S, Wessendorf S, Berger H, Hummel M, et al. Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma. Haematol. 2008;93:688–96.
doi: 10.3324/haematol.12057
Kridel R, Mottok A, Farinha P, Ben-Neriah S, Ennishi D, Zheng Y, et al. Cell of origin of transformed follicular lymphoma. Blood. 2015;126:2118–27.
pubmed: 26307535
pmcid: 4626253
doi: 10.1182/blood-2015-06-649905
Tobin JWD, Keane C, Gunawardana J, Mollee P, Birch S, Hoang T, et al. Progression of disease within 24 months in follicular lymphoma is associated with reduced intratumoral immune infiltration. J Clin Oncol. 2019;37:3300–9.
pubmed: 31461379
pmcid: 6881104
doi: 10.1200/JCO.18.02365