Format

Send to

Choose Destination
Blood. 2016 Jun 16;127(24):3026-34. doi: 10.1182/blood-2015-12-686550. Epub 2016 Mar 30.

Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas.

Author information

1
Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden;
2
Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden; BGI-Shenzhen, Shenzhen, China;
3
Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden;
4
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;
5
Department of Genetics, Portuguese Oncology Institute, and Abel Salazar Biomedical Sciences Institute, Porto University, Porto, Portugal;
6
Institute for Cancer Genetics, Columbia University, New York, NY;
7
BGI-Shenzhen, Shenzhen, China;
8
State Key Laboratory of Oncology in South China and Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China;
9
Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China;
10
Department of Pathology and Cell Biology, Columbia University, New York, NY;
11
Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden; and.
12
Department of Immunology, Genetics and Pathology, Rudbecklaboratoriet, Uppsala University, Uppsala, Sweden.

Abstract

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.

PMID:
27030389
DOI:
10.1182/blood-2015-12-686550
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center