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Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas
Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden.;BGI Shenzhen, Shenzhen, Peoples R China..
Karolinska Inst, Dept Biosci & Nutr, Solna, Sweden..
Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
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2016 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 24, 3026-3034 p.Article in journal (Refereed) PublishedText
Abstract [en]

Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2. Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort. Collectively, a subset of samples was found to be affected by gains (12%), amplifications (3%), and translocations (4%) of the PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed that these cytogenetic alterations correlated with increased expression of PD-L1 but not of PD-L2. Moreover, cytogenetic alterations affecting the PD-L1/PD-L2 locus were more frequently observed in the non-germinal center B cell-like (non-GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1 overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD-L2 axis might benefit DLBCL patients, especially those belonging to the more aggressive non-GCB subtype.

Place, publisher, year, edition, pages
2016. Vol. 127, no 24, 3026-3034 p.
National Category
Hematology
Identifiers
URN: urn:nbn:se:uu:diva-299719DOI: 10.1182/blood-2015-12-686550ISI: 000378337100016PubMedID: 27030389OAI: oai:DiVA.org:uu-299719DiVA: diva2:950007
Funder
Swedish Cancer SocietySwedish Research CouncilEU, European Research CouncilSwedish Childhood Cancer Foundation
Available from: 2016-07-26 Created: 2016-07-26 Last updated: 2016-07-26Bibliographically approved

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