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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Georgiou, K (Author) Other; Chen, LY (Author) Other; Berglund, M (Author) Other; Ren, WC (Author) Other; de Miranda, NFCC (Author) Other; Lisboa, S (Author) Other; Fangazio, M (Author) Other; Zhu, SD (Author) Other; Hou, Y (Author) Other; Wu, K (Author) Other; Fang, WF (Author) Other; Wang, XH (Author) Other; Meng, B (Author) Other; Zhang, L (Author) Other; Zeng, YX (Author) Other; Bhagat, G (Author) Other; Nordenskjold, M (Author) Other; Sundstrom, C (Author) Other; Enblad, G (Author) Other; Dalla Favera, R (Author) Other; Zhang, HL (Author) Other; Manuel R Teixeira (Author) ICBAS; Pasqualucci, L (Author) Other; Peng, RJ (Author) Other; Pan Hammarstrom, Q (Author) Other

Journal

Title: Blood

Vol. 127

Pages: 3026-3034

ISSN: 0006-4971

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 119 Citations

Scopus - 122 Citations

Other information

Authenticus ID: P-00K-MB3

DOI: 10.1182/blood-2015-12-686550

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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9