Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes (original) (raw)

• Basso, K. & Dalla-Favera, R. Germinal centres and B cell lymphomagenesis. Nat. Rev. Immunol. 15, 172–184 (2015).
  CAS PubMed Google Scholar
• Monti, S. et al. Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma. Cancer Cell 22, 359–372 (2012).
  CAS PubMed PubMed Central Google Scholar
• Pasqualucci, L. et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat. Genet. 43, 830–837 (2011).
  CAS PubMed PubMed Central Google Scholar
• Morin, R. D. et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 476, 298–303 (2011).
  CAS PubMed PubMed Central Google Scholar
• Lohr, J. G. et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. USA 109, 3879–3884 (2012).
  CAS PubMed PubMed Central Google Scholar
• Morin, R. D. et al. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood 122, 1256–1265 (2013).
  CAS PubMed PubMed Central Google Scholar
• de Miranda, N. F. et al. Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients. Blood 124, 2544–2553 (2014).
  PubMed PubMed Central Google Scholar
• Reddy, A. et al. Genetic and functional drivers of diffuse large B cell lymphoma. Cell 171, 481–494.e15 (2017).
  CAS PubMed PubMed Central Google Scholar
• Rosenwald, A. et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 346, 1937–1947 (2002).
  PubMed Google Scholar
• Monti, S. et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 105, 1851–1861 (2005).
  CAS PubMed Google Scholar
• Ngo, V. N. et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 470, 115–119 (2011).
  CAS PubMed Google Scholar
• Caro, P. et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 22, 547–560 (2012).
  CAS PubMed PubMed Central Google Scholar
• Davis, R. E. et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463, 88–92 (2010).
  CAS PubMed PubMed Central Google Scholar
• Chen, L. et al. SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas. Cancer Cell 23, 826–838 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lenz, G. et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319, 1676–1679 (2008).
  CAS PubMed Google Scholar
• Muppidi, J. R. et al. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature 516, 254–258 (2014).
  CAS PubMed PubMed Central Google Scholar
• Morin, R. D. et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet. 42, 181–185 (2010).
  CAS PubMed PubMed Central Google Scholar
• Pfeifer, M. et al. PTEN loss defines a PI3K/AKT pathway–dependent germinal center subtype of diffuse large B-cell lymphoma. Proc. Natl. Acad. Sci. USA 110, 12420–12425 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lenz, G. et al. Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med. 359, 2313–2323 (2008).
  CAS PubMed PubMed Central Google Scholar
• Dubois, S. et al. Biological and clinical relevance of associated genomic alterations in MYD88 L265P and non-L265P-mutated diffuse large B-cell lymphoma: analysis of 361 cases. Clin. Cancer Res. 23, 2232–2244 (2017).
  CAS PubMed Google Scholar
• Ennishi, D. et al. Genetic profiling of MYC and BCL2 in diffuse large B-cell lymphoma determines cell-of-origin-specific clinical impact. Blood 129, 2760–2770 (2017).
  CAS PubMed Google Scholar
• Pfreundschuh, M. et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 9, 105–116 (2008).
  CAS PubMed Google Scholar
• Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214–218 (2013).
  CAS PubMed PubMed Central Google Scholar
• Kamburov, A. et al. Comprehensive assessment of cancer missense mutation clustering in protein structures. Proc. Natl. Acad. Sci. USA 112, E5486–E5495 (2015).
  CAS PubMed PubMed Central Google Scholar
• Kasar, S. et al. Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution. Nat. Commun. 6, 8866 (2015).
  CAS PubMed Google Scholar
• Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
  CAS PubMed PubMed Central Google Scholar
• Pasqualucci, L. et al. AID is required for germinal center-derived lymphomagenesis. Nat. Genet. 40, 108–112 (2008).
  CAS PubMed Google Scholar
• Chapuy, B. et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 127, 869–881 (2016).
  CAS PubMed PubMed Central Google Scholar
• Georgiou, K. et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood 127, 3026–3034 (2016).
  CAS PubMed Google Scholar
• Scott, D. W. et al. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood 119, 4949–4952 (2012).
  CAS PubMed PubMed Central Google Scholar
• Challa-Malladi, M. et al. Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20, 728–740 (2011).
  CAS PubMed PubMed Central Google Scholar
• Green, M. R. et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 116, 3268–3277 (2010).
  CAS PubMed PubMed Central Google Scholar
• Steidl, C. et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 471, 377–381 (2011).
  CAS PubMed PubMed Central Google Scholar
• Brunet, J. P., Tamayo, P., Golub, T. R. & Mesirov, J. P. Metagenes and molecular pattern discovery using matrix factorization. Proc. Natl. Acad. Sci. USA 101, 4164–4169 (2004).
  CAS PubMed PubMed Central Google Scholar
• Dierlamm, J. 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. Haematologica 93, 688–696 (2008).
  CAS PubMed Google Scholar
• Lenz, G. et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc. Natl. Acad. Sci. USA 105, 13520–13525 (2008).
  CAS PubMed PubMed Central Google Scholar
• Pham-Ledard, A. et al. High frequency and clinical prognostic value of MYD88 L265P mutation in primary cutaneous diffuse large B-cell lymphoma, leg-type. JAMA Dermatol. 150, 1173–1179 (2014).
  PubMed Google Scholar
• Rovira, J. et al. MYD88 L265P mutations, but no other variants, identify a subpopulation of DLBCL patients of activated B-cell origin, extranodal involvement, and poor outcome. Clin. Cancer Res. 22, 2755–2764 (2016).
  CAS PubMed Google Scholar
• Rossi, D. et al. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J. Exp. Med. 209, 1537–1551 (2012).
  CAS PubMed PubMed Central Google Scholar
• Spina, V. et al. The genetics of nodal marginal zone lymphoma. Blood 128, 1362–1373 (2016).
  CAS PubMed PubMed Central Google Scholar
• Zhang, Q. et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22; q32). Nat. Genet. 22, 63–68 (1999).
  CAS PubMed Google Scholar
• Kiel, M. J. et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J. Exp. Med. 209, 1553–1565 (2012).
  CAS PubMed PubMed Central Google Scholar
• Flossbach, L. et al. BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Int. J. Cancer 129, 70–77 (2011).
  CAS PubMed Google Scholar
• Zucca, E., Bertoni, F., Vannata, B. & Cavalli, F. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas. Clin. Cancer Res. 20, 5207–5216 (2014).
  CAS PubMed Google Scholar
• MacLennan, I. C. et al. Extrafollicular antibody responses. Immunol. Rev. 194, 8–18 (2003).
  CAS PubMed Google Scholar
• Erdmann, T. et al. Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL. Blood 130, 310–322 (2017).
  CAS PubMed Google Scholar
• Sun, Z. et al. PTEN C-terminal deletion causes genomic instability and tumor development. Cell Reports 6, 844–854 (2014).
  CAS PubMed Google Scholar
• Ortega-Molina, A. et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat. Med. 21, 1199–1208 (2015).
  CAS PubMed PubMed Central Google Scholar
• Boice, M. et al. Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T cells. Cell 167, 405–418.e413 (2016).
  CAS PubMed PubMed Central Google Scholar
• Ying, C. Y. et al. MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma. Nat. Immunol. 14, 1084–1092 (2013).
  CAS PubMed PubMed Central Google Scholar
• Zhang, J. et al. The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in B-cell lymphoma. Cancer Discov. 7, 322–337 (2017).
  PubMed PubMed Central Google Scholar
• Krysiak, K. et al. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood 129, 473–483 (2017).
  CAS PubMed PubMed Central Google Scholar
• Béguelin, W. et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23, 677–692 (2013).
  PubMed PubMed Central Google Scholar
• Li, H. et al. Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. Blood 123, 1487–1498 (2014).
  CAS PubMed PubMed Central Google Scholar
• Okosun, J. et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat. Genet. 46, 176–181 (2014).
  CAS PubMed Google Scholar
• Yang, S. M., Kim, B. J., Norwood Toro, L. & Skoultchi, A. I. H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation. Proc. Natl. Acad. Sci. USA 110, 1708–1713 (2013).
  CAS PubMed PubMed Central Google Scholar
• Xu-Monette, Z. Y. et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood 120, 3986–3996 (2012).
  CAS PubMed PubMed Central Google Scholar
• Sesques, P. & Johnson, N. A. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood 129, 280–288 (2017).
  CAS PubMed Google Scholar
• Li, Y., Choi, P. S., Casey, S. C., Dill, D. L. & Felsher, D. W. MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state. Cancer Cell 26, 262–272 (2014).
  CAS PubMed PubMed Central Google Scholar
• Landau, D. A. et al. Mutations driving CLL and their evolution in progression and relapse. Nature 526, 525–530 (2015).
  CAS PubMed PubMed Central Google Scholar
• Novak, A. J. et al. Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma. Blood Cancer J. 5, e346 (2015).
  CAS PubMed PubMed Central Google Scholar
• Chapman, M. A. et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471, 467–472 (2011).
  CAS PubMed PubMed Central Google Scholar
• Fisher, S. et al. A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries. Genome Biol. 12, R1 (2011).
  PubMed PubMed Central Google Scholar
• Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat. Biotechnol. 27, 182–189 (2009).
  CAS PubMed PubMed Central Google Scholar
• McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
  CAS PubMed PubMed Central Google Scholar
• Lichtenstein, L., Wood, B., MacBeth, A., Birsoy, O. & Lennon, N. ReCapSeg: Validation of somatic copy number alterations for CLIA whole exome sequencing. Cancer Res. 76 Supplement, abstr. 3641 (2016).
• Giannikou, K. et al. Whole exome sequencing identifies TSC1/TSC2 biallelic loss as the primary and sufficient driver event for renal angiomyolipoma development. PLoS Genet. 12, e1006242 (2016).
  PubMed PubMed Central Google Scholar
• Burger, J. A. et al. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. Nat. Commun. 7, 11589 (2016).
  CAS PubMed PubMed Central Google Scholar
• Mermel, C. H. et al. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 12, R41 (2011).
  PubMed PubMed Central Google Scholar
• Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013).
  CAS PubMed PubMed Central Google Scholar
• Ramos, A. H. et al. Oncotator: cancer variant annotation tool. Hum. Mutat. 36, E2423–E2429 (2015).
  PubMed PubMed Central Google Scholar
• Costello, M. et al. Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation. Nucleic Acids Res. 41, e67 (2013).
  CAS PubMed PubMed Central Google Scholar
• Giannakis, M. et al. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Reports 17, 1206 (2016).
  CAS PubMed Google Scholar
• Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 159, 676–690 (2014).
  Google Scholar
• DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).
  CAS PubMed PubMed Central Google Scholar
• Carter, S. L. et al. Absolute quantification of somatic DNA alterations in human cancer. Nat. Biotechnol. 30, 413–421 (2012).
  CAS PubMed PubMed Central Google Scholar
• Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).
  CAS PubMed PubMed Central Google Scholar
• Abo, R. P. et al. BreaKmer: detection of structural variation in targeted massively parallel sequencing data using kmers. Nucleic Acids Res. 43, e19 (2015).
  PubMed Google Scholar
• Layer, R. M., Chiang, C., Quinlan, A. R. & Hall, I. M. LUMPY: a probabilistic framework for structural variant discovery. Genome Biol. 15, R84 (2014).
  PubMed PubMed Central Google Scholar
• Wala, J. A. et al. SvABA: genome-wide detection of structural variants and indels by local assembly. Genome Res. 28, 581–591 (2018).
  Article PubMed PubMed Central Google Scholar