Author Affiliations
- Bianca Schuhmacher1,
- Julia Bein1,
- Tobias Rausch2,3,
- Vladimir Benes2,
- Thomas Tousseyn4,
- Martine Vornanen5,
- Maurilio Ponzoni6,
- Lorenz Thurner7,8,
- Randy Gascoyne9,
- Christian Steidl9,
- Ralf Küppers10,11,
- Martin-Leo Hansmann1,12,13 and
- Sylvia Hartmann1,12⇑
- 1Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany
- 2Genecore, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- 3Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- 4Department of Pathology, University Hospitals K.U. Leuven, Belgium
- 5Department of Pathology, Tampere University Hospital and University of Tampere, Finland
- 6Unit of Lymphoid Malignancies, Department of Pathology, Scientific Institute San Raffaele, Milan, Italy
- 7José Carreras Center for Immuno and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg, Saar, Germany
- 8Department of Internal Medicine 2, Hospital of the J. W. Goethe University, Frankfurt am Main, Germany
- 9Department of Pathology and Laboratory Medicine and the Centre for Lymphoid Cancer, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada
- 10Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
- 11Deutsches Konsortium für Translationale Krebsforschung (DKTK), Germany
- 12Reference and Consultant Center for Lymphoma and Lymph Node Diagnostics, Goethe University, Frankfurt am Main, Germany
- 13Frankfurt Institute of Advanced Studies, Frankfurt am Main, Germany
- Correspondence:
s.hartmann{at}em.uni-frankfurt.de
Data supplements
Schuhmacher et al. Supplementary Appendix
Schuhmacher et al. Supplementary appendix provided by the authors.
Files in this Data Supplement:
Disclosures and Contributions
Files in this Data Supplement:
ARTICLE FIGURES & DATA
Figures
- Figure 1.
Genes recurrently affected by mutations and their mutational load in nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. (A) Frequencies of recurrently mutated genes (≥2 cases) in six cases of NLPHL A/B (blue), 11 cases of NLPHL C/D/E (green) and nine cases of THRLBCL (red) sorted by overall recurrence. (B) Mutated genes per case in NLPHL A/B, NLPHL C/D/E and THRLBCL. (C) Number of SNVs per case in NLPHL A/B, NLPHL C/D/E and THRLBCL. (D) Scatter plot of SNVs per case and kbp of CCDS in the seven most recurrently mutated genes in NLPHL A/B, NLPHL C/D/E and THRL-BCL. In (B-D), horizontal lines correspond to medians; P-values by Kruskal-Wallis test are indicated in the case of statistical significance. *P<0.05, **P<0.01, ***P<0.001. NLPHL: nodular lymphocyte-predominant Hodgkin lymphoma; THRLBCL: T-cell/histiocyte-rich large B-cell lymphoma; SNVs: single nucleotide variants; CCDS: Consensus coding sequence.
- Figure 2.
Mutation patterns in the most recurrently mutated genes in nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. Schematic overview of the mutational distribution in the most recurrently mutated genes. For each gene missense (triangles), stop gain (spheres) and splice site (squares) mutations are mapped to coding exons (top) and protein domains (bottom). Mutations are color-coded according to the occurrence in the groups (blue: NLPHL A/B; green: NLPHL C/D/E; red: THRLBCL). Amino acid positions of protein domains are adopted from the Uniprot database (www.uniprot.org) and refer to the canonical sequences (JUNB: P17275, DUSP2: Q05923, SGK1: O00141, SOCS1: O15524, CREBBP: Q92793, FN1: P02751, TRRAP: Q9Y4A5). bZIP: basic leucine zipper motif; DsPc: dual specific phosphatase, catalytic domain; Pkinase: protein kinase domain; AGC-kinase C: AGC-kinase C-terminal domain; Rhod: rhodanese; SH2: Src homology 2 domain; KIR: kinase inhibitory region; CH1/2/3: cysteine/hystidine-rich region; KIX: kinase inducible domain; BROMO: bromodomain; HAT: histone acetyltransferase domain; Q: poly glutamine stretch; FN: fibronectin; TP53: tumor suppressor p53 binding site; FAT: FRAP-ATM-TRRAP domain; FATC: FAT C-terminal; PI3K/PI4K: phosphatidylinositol 3-kinase/phosphatidylinositol 4-kinase domain; NLPHL: nodular lymphocyte-predominant Hodgkin lymphoma; THRLBCL: T-cell/histiocyte-rich large B-cell lymphoma.
- Figure 3.
Characteristics of somatic mutations and activation-induced cytidine deaminase expression in nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. (A) Analysis of distribution of mutations to SHM hotspot motifs. (B) Ratio of mutations at C:G sites to A:T sites. (C) Ratio of transition to transversion mutations. In (A-C) synonymous SNVs were considered in addition to non-synonymous SNVs. Asterisks denote statistical significance. *P<0.05, **P<0.01, ***P<0.001. P-values by χ2 test. (D) Expression of AICDA in the LP cells of NLPHL (400× magnification). (E) Expression of AICDA in the tumor cells of THRLBCL (400× magnification). Tumor cells are highlighted by arrows. AICDA: activation-induced cytidine deaminase; NLPHL: nodular lymphocyte-predominant Hodgkin lymphoma; THRLBCL: T-cell/histiocyte-rich large B-cell lymphoma; SHM: somatic hypermutation; SNVs: single nucleotide variants.
Tables
- Table 1.
Clinical information on nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma patients.
Vol 104 Issue 2
