Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma.
The pathogenesis of primary mediastinal large B-cell lymphoma (PMBCL) is incompletely understood. Recently, specific genotypic and phenotypic features have been linked to tumor cell immune escape mechanisms in PMBCL. We studied 571 B-cell lymphomas with a focus on PMBCL. Using fluorescence in situ hybridization here, we report that the programmed death ligand (PDL) locus (9p24.1) is frequently and specifically rearranged in PMBCL (20%) as compared with diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma. Rearrangement was significantly correlated with overexpression of PDL transcripts. Utilizing high-throughput sequencing techniques, we characterized novel translocations and chimeric fusion transcripts involving PDLs at base-pair resolution. Our data suggest that recurrent genomic rearrangement events underlie an immune privilege phenotype in a subset of B-cell lymphomas.
Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, BC, Canada; and.
David D W
DD
Twa
Fong Chun
FC
Chan
Susana
S
Ben-Neriah
Bruce W
BW
Woolcock
Anja
A
Mottok
King L
KL
Tan
Graham W
GW
Slack
Jay
J
Gunawardana
Raymond S
RS
Lim
Andrew W
AW
McPherson
Robert
R
Kridel
Adele
A
Telenius
David W
DW
Scott
Kerry J
KJ
Savage
Sohrab P
SP
Shah
Randy D
RD
Gascoyne
Christian
C
Steidl
D060890:B7-H1 Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D002899:Chromosomes, Human, Pair 9; D056915:DNA Copy Number Variations; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000453:epidemiology / Q000235:genetics*; D008479:Mediastinal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics*; D014178:Translocation, Genetic
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein