Detailed Molecular and Immune Marker Profiling of Archival Prostate Cancer Samples Reveals an Inverse Association between TMPRSS2:ERG Fusion Status and Immune Cell Infiltration

Siegel, 2014, Cancer statistics, 2014, CA Cancer J Clin, 64, 9, 10.3322/caac.21208 2015, The molecular taxonomy of primary prostate cancer, Cell, 163, 1011, 10.1016/j.cell.2015.10.025 Wedge, 2018, Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets, Nat Genet, 50, 682, 10.1038/s41588-018-0086-z Bryant, 2017, Overcoming oncogenic mediated tumor immunity in prostate cancer, Int J Mol Sci, 18, 1542, 10.3390/ijms18071542 Fridman, 2012, The immune contexture in human tumours: impact on clinical outcome, Nat Rev Cancer, 12, 298, 10.1038/nrc3245 Sciarra, 2016, Prognostic value of inflammation in prostate cancer progression and response to therapeutic: a critical review, J Inflamm (Lond), 13, 35, 10.1186/s12950-016-0143-2 Linch, 2017, Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters, Ann Oncol, 28, 2472, 10.1093/annonc/mdx355 Dominguez-Valentin, 2016, Frequent mismatch-repair defects link prostate cancer to Lynch syndrome, BMC Urol, 16, 15, 10.1186/s12894-016-0130-1 Hempelmann, 2018, Microsatellite instability in prostate cancer by PCR or next-generation sequencing, J Immunother Cancer, 6, 29, 10.1186/s40425-018-0341-y Kalina, 2017, Mutational analysis of gene fusions predicts novel MHC class I-restricted T cell epitopes & immune signatures in a subset of prostate cancer, Clin Cancer Res, 23, 7596, 10.1158/1078-0432.CCR-17-0618 Zhang, 2017, INTEGRATE-neo: a pipeline for personalized gene fusion neoantigen discovery, Bioinformatics, 33, 555, 10.1093/bioinformatics/btw674 Ferraldeschi, 2015, PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate, Eur Urol, 67, 795, 10.1016/j.eururo.2014.10.027 Gevensleben, 2016, The immune checkpoint regulator PD-L1 is highly expressed in aggressive primary prostate cancer, Clin Cancer Res, 22, 1969, 10.1158/1078-0432.CCR-15-2042 Sung, 2016, Correlation of ERG immunohistochemistry with molecular detection of TMPRSS2-ERG gene fusion, J Clin Pathol, 69, 586, 10.1136/jclinpath-2015-203314 Zlobec, 2009, Invasive front of colorectal cancer: dynamic interface of pro-/anti-tumor factors, World J Gastroenterol, 15, 5898, 10.3748/wjg.15.5898 Eijkelenboom, 2016, Reliable next-generation sequencing of formalin-fixed, paraffin-embedded tissue using single molecule tags, J Mol Diagn, 18, 851, 10.1016/j.jmoldx.2016.06.010 Boyle, 2014, MIPgen: optimized modeling and design of molecular inversion probes for targeted resequencing, Bioinformatics, 30, 2670, 10.1093/bioinformatics/btu353 Gonzalez-Perez, 2013, IntOGen-mutations identifies cancer drivers across tumor types, Nat Methods, 10, 1081, 10.1038/nmeth.2642 Wilm, 2012, LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets, Nucleic Acids Res, 40, 11189, 10.1093/nar/gks918 McKenna, 2010, The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data, Genome Res, 20, 1297, 10.1101/gr.107524.110 Cibulskis, 2013, Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples, Nat Biotechnol, 31, 213, 10.1038/nbt.2514 McLaren, 2016, The ensembl variant effect predictor, Genome Biol, 17, 122, 10.1186/s13059-016-0974-4 Dobin, 2013, STAR: ultrafast universal RNA-seq aligner, Bioinformatics, 29, 15, 10.1093/bioinformatics/bts635 Haas, 2017, STAR-fusion: fast and accurate fusion transcript detection from RNA-seq, bioRxiv, 120295 Lågstad, 2017, chimeraviz: A tool for visualizing chimeric RNA, Bioinformatics, 33, 2954, 10.1093/bioinformatics/btx329 Patro, 2017, Salmon: fast and bias-aware quantification of transcript expression using dual-phase inference, Nat Methods, 14, 417, 10.1038/nmeth.4197 Soneson, 2016, Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences, F1000Res, 4, 1521, 10.12688/f1000research.7563.2 Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol, 15, 550, 10.1186/s13059-014-0550-8 Subramanian, 2005, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc Natl Acad Sci U S A, 102, 15545, 10.1073/pnas.0506580102 Liberzon, 2011, Molecular signatures database (MSigDB) 3.0, Bioinformatics, 27, 1739, 10.1093/bioinformatics/btr260 Boegel, 2012, HLA typing from RNA-Seq sequence reads, Genome Med, 4, 102, 10.1186/gm403 Hundal, 2016, pVAC-Seq: a genome-guided in silico approach to identifying tumor neoantigens, Genome Med, 8, 11, 10.1186/s13073-016-0264-5 Nielsen, 2007, NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence, PLoS One, 2, e796, 10.1371/journal.pone.0000796 Karosiene, 2013, NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ, Immunogenetics, 65, 711, 10.1007/s00251-013-0720-y Niu, 2014, MSIsensor: microsatellite instability detection using paired tumor-normal sequence data, Bioinformatics, 30, 1015, 10.1093/bioinformatics/btt755 Galon, 2006, Type, density, and location of immune cells within human colorectal tumors predict clinical outcome, Science, 313, 1960, 10.1126/science.1129139 Galon, 2012, Cancer classification using the Immunoscore: a worldwide task force, J Transl Med, 10, 205, 10.1186/1479-5876-10-205 Yu, 2014, Novel fusion transcripts associate with progressive prostate cancer, Am J Pathol, 184, 2840, 10.1016/j.ajpath.2014.06.025 Scolnick, 2015, An efficient method for identifying gene fusions by targeted RNA sequencing from fresh frozen and FFPE samples, PLoS One, 10, e0128916, 10.1371/journal.pone.0128916 Dunning, 2017, Mining human prostate cancer datasets: the “camcAPP” shiny app, EBioMedicine, 17, 5, 10.1016/j.ebiom.2017.02.022 Kaur, 2018, Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer, Mod Pathol, 31, 1539, 10.1038/s41379-018-0083-x Flammiger, 2012, Intratumoral T but not B lymphocytes are related to clinical outcome in prostate cancer, APMIS, 120, 901, 10.1111/j.1600-0463.2012.02924.x Shan, 2018, TMPRSS2-ERG fusion promotes recruitment of regulatory T cells and tumor growth in prostate cancer, Am J Med Sci, 356, 72, 10.1016/j.amjms.2018.03.023 Marty, 2018, Evolutionary pressure against MHC class II binding cancer mutations, Cell, 175, 416, 10.1016/j.cell.2018.08.048 McGrail, 2018, Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers, Nat Commun, 9, 1317, 10.1038/s41467-018-03730-x Smits, 2014, The estimation of tumor cell percentage for molecular testing by pathologists is not accurate, Mod Pathol, 27, 168, 10.1038/modpathol.2013.134 Buisseret, 2017, Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer, Mod Pathol, 30, 1204, 10.1038/modpathol.2017.43 Saltz, 2018, Spatial organization and molecular correlation of tumor-infiltrating lymphocytes using deep learning on pathology images, Cell Rep, 23, 181, 10.1016/j.celrep.2018.03.086 Qu, 2018, Immunological approaches towards cancer and inflammation: a cross talk, Front Immunol, 9, 563, 10.3389/fimmu.2018.00563 Robbe, 2018, Clinical whole-genome sequencing from routine formalin-fixed, paraffin-embedded specimens: pilot study for the 100,000 Genomes Project, Genet Med, 20, 1196, 10.1038/gim.2017.241 Tomlins, 2008, The role of SPINK1 in ETS rearrangement-negative prostate cancers, Cancer Cell, 13, 519, 10.1016/j.ccr.2008.04.016 Kumar, 2014, Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes, Genome Biol, 15, 530, 10.1186/s13059-014-0530-z Neveling, 2017, BRCA testing by single-molecule molecular inversion probes, Clin Chem, 63, 503, 10.1373/clinchem.2016.263897 Ong, 2018, A gene signature associated with PTEN activation defines good prognosis intermediate risk prostate cancer cases, J Pathol Clin Res, 4, 103, 10.1002/cjp2.94 Gopalan, 2013, TMPRSS2-ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry, Histopathology, 63, 279, 10.1111/his.12153 Gopalan, 2009, TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy, Cancer Res, 69, 1400, 10.1158/0008-5472.CAN-08-2467 Dal Pra, 2013, TMPRSS2-ERG status is not prognostic following prostate cancer radiotherapy: implications for fusion status and DSB repair, Clin Cancer Res, 19, 5202, 10.1158/1078-0432.CCR-13-1049