PMID- 25712539 OWN - NLM STAT- MEDLINE DCOM- 20150720 LR - 20171116 IS - 1096-9896 (Electronic) IS - 0022-3417 (Linking) VI - 236 IP - 2 DP - 2015 Jun TI - Recurrent genomic rearrangements in primary testicular lymphoma. PG - 136-41 LID - 10.1002/path.4522 [doi] AB - Primary testicular diffuse large B cell lymphoma (PTL) is an aggressive malignancy that occurs in the immune-privileged anatomical site of the testis. We have previously shown that structural genomic rearrangements involving the MHC class II transactivator CIITA and programmed death ligands (PDLs) 1 and 2 are frequent across multiple B cell lymphoma entities. Specifically in PTL, we found rearrangements in the PDL locus by fluorescence in situ hybridization (FISH). However, breakpoint anatomy and rearrangement partners were undetermined, while CIITA rearrangements had not been reported previously in PTL. Here, we performed bacterial artificial chromosome capture sequencing on three archival, formalin-fixed, paraffin-embedded tissue biopsies, interrogating 20 known rearrangement hotspots in B cell lymphomas. We report novel CIITA, FOXP1 and PDL rearrangements involving IGHG4, FLJ45248, RFX3, SMARCA2 and SNX29. Moreover, we present immunohistochemistry data supporting the association between PDL rearrangements and increased protein expression. Finally, using FISH, we show that CIITA (8/82; 10%) and FOXP1 (5/74; 7%) rearrangements are recurrent in PTL. In summary, we describe rearrangement frequencies and novel rearrangement partners of the CIITA, FOXP1 and PDL loci at base-pair resolution in a rare, aggressive lymphoma. Our data suggest immune-checkpoint inhibitor therapy as a promising intervention for PTL patients harbouring PDL rearrangements. CI - Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. FAU - Twa, David D W AU - Twa DD AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. FAU - Mottok, Anja AU - Mottok A AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. FAU - Chan, Fong Chun AU - Chan FC AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Bioinformatics Training Programme, University of British Columbia, Vancouver, BC, Canada. FAU - Ben-Neriah, Susana AU - Ben-Neriah S AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. FAU - Woolcock, Bruce W AU - Woolcock BW AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. FAU - Tan, King L AU - Tan KL AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. FAU - Mungall, Andrew J AU - Mungall AJ AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada. FAU - McDonald, Helen AU - McDonald H AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada. FAU - Zhao, Yongjun AU - Zhao Y AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada. FAU - Lim, Raymond S AU - Lim RS AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. FAU - Nelson, Brad H AU - Nelson BH AD - Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada. AD - Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. FAU - Milne, Katy AU - Milne K AD - Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada. FAU - Shah, Sohrab P AU - Shah SP AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Bioinformatics Training Programme, University of British Columbia, Vancouver, BC, Canada. FAU - Morin, Ryan D AU - Morin RD AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, Canada. FAU - Marra, Marco A AU - Marra MA AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada. FAU - Scott, David W AU - Scott DW AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. FAU - Gascoyne, Randy D AU - Gascoyne RD AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. FAU - Steidl, Christian AU - Steidl C AD - Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada. AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150326 PL - England TA - J Pathol JT - The Journal of pathology JID - 0204634 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (FOXP1 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (MHC class II transactivator protein) RN - 0 (Nuclear Proteins) RN - 0 (PDCD1LG2 protein, human) RN - 0 (Programmed Cell Death 1 Ligand 2 Protein) RN - 0 (Repressor Proteins) RN - 0 (Trans-Activators) SB - IM MH - B7-H1 Antigen/*genetics MH - Chromosome Breakpoints MH - Chromosomes, Artificial, Bacterial MH - Forkhead Transcription Factors/*genetics MH - Gene Deletion MH - Gene Rearrangement, B-Lymphocyte/*genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Large B-Cell, Diffuse/*genetics MH - Male MH - Nuclear Proteins/genetics MH - Programmed Cell Death 1 Ligand 2 Protein/*genetics MH - Recurrence MH - Repressor Proteins/*genetics MH - Testicular Neoplasms/*genetics MH - Trans-Activators/genetics MH - Translocation, Genetic/genetics OTO - NOTNLM OT - CD274 OT - CIITA OT - FOXP1 OT - PDCD1LG2 OT - capture sequencing OT - fluorescence in situ hybridization (FISH) OT - genomic rearrangements OT - primary testicular lymphoma (PTL) OT - programmed death ligands EDAT- 2015/02/26 06:00 MHDA- 2015/07/21 06:00 CRDT- 2015/02/26 06:00 PHST- 2014/12/15 00:00 [received] PHST- 2015/02/05 00:00 [revised] PHST- 2015/02/18 00:00 [accepted] PHST- 2015/02/26 06:00 [entrez] PHST- 2015/02/26 06:00 [pubmed] PHST- 2015/07/21 06:00 [medline] AID - 10.1002/path.4522 [doi] PST - ppublish SO - J Pathol. 2015 Jun;236(2):136-41. doi: 10.1002/path.4522. Epub 2015 Mar 26.