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MOESM1 of Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies

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Version 2 2019-11-13, 05:05
Version 1 2019-10-23, 08:24
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posted on 2019-11-13, 05:05 authored by Zijun Xu-Monette, Jianyong Li, Yi Xia, Beryl Crossley, Robert Bremel, Yi Miao, Min Xiao, Thomas Snyder, Ganiraju Manyam, Xiaohong Tan, Hongwei Zhang, Carlo Visco, Alexandar Tzankov, Karen Dybkaer, Govind Bhagat, Wayne Tam, Hua You, Eric Hsi, J. Krieken, Jooryung Huh, Maurilio Ponzoni, Andrés Ferreri, Michael Møller, Miguel Piris, Jane Winter, Jeffrey Medeiros, Bing Xu, Yong Li, Ilan Kirsch, Ken Young
Additional file 1: Fig S1.. Construction and clinical outcome of the diffuse large B-cell lymphoma (DLBCL) cohort. Fig. S2. Diagram showing numbers of cases in this mutation study that have been characterized by various biomarker studies, and survival rates of patients whose sequencing results were correlated with prognosis. Fig. S3. CONSORT flow diagram illustrating the number of cases performed for high-throughput IG sequencing and clonal sequence analysis. Fig. S4. Molecular characterization for immunoglobulin heavy chain (IGH) gene usage in the study cohort. Fig. S5. Immunoglobulin heavy chain V gene (IGHV) somatic hypermutation (SHM) analysis. Fig. S6. Analysis for length of heavy chain CDR3. Fig. S7. Prediction of MHC-binding peptides and frequency of T-cell exposed motifs (TCEM) for immunoglobulin diagnostic sequences in the training set and validation set. (a) Regional distribution of relatively rare neoantigens derived from heavy chain and light chain immunoglobulin genes in DLBCL patients in the training set (top) and validation set (bottom). (b) Cases with high degree of heavy chain or light chain IGV SHM compared with cases without had higher frequency of relatively rare TCEM in the training (left) and validation sets (right). (c) In ABC-DLBCL, high IGV SHM was associated with lower tissue cellularity of CD4+ T cells. Fig. S8. Moleclar analysis for immunoglobulin heavy chain ongoing SHM and light chain SHM. Fig. S9. Immunoglobulin light chain SHM and CDR3 analysis. Fig S10. Comparison between different subsets of DLBCL. Fig S11. Light chain IGK/LV ongoing SHM analysis.

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