Undifferentiated nasopharyngeal carcinoma from a nonendemic area: protective role of HLA allele products presenting conserved EBV epitopes

Pasini, Elisa, Caggiari, Laura, Dal Maso, Luigino, Martorelli, Debora, Guidoboni, Massimo, Vaccher, Emanuela, Barzan, Luigi, Franchin, Giovanni, Gloghini, Annunziata, De Re, Valli, Sacchi, Nicoletta, Serraino, Diego, Carbone, Antonino, Rosato, Antonio and Dolcetti, Riccardo (2009) Undifferentiated nasopharyngeal carcinoma from a nonendemic area: protective role of HLA allele products presenting conserved EBV epitopes. International Journal of Cancer, 125 6: 1358-1364. doi:10.1002/ijc.24515


Author Pasini, Elisa
Caggiari, Laura
Dal Maso, Luigino
Martorelli, Debora
Guidoboni, Massimo
Vaccher, Emanuela
Barzan, Luigi
Franchin, Giovanni
Gloghini, Annunziata
De Re, Valli
Sacchi, Nicoletta
Serraino, Diego
Carbone, Antonino
Rosato, Antonio
Dolcetti, Riccardo
Title Undifferentiated nasopharyngeal carcinoma from a nonendemic area: protective role of HLA allele products presenting conserved EBV epitopes
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
1097-0215
Publication date 2009-09-15
Sub-type Article (original research)
DOI 10.1002/ijc.24515
Open Access Status Not yet assessed
Volume 125
Issue 6
Start page 1358
End page 1364
Total pages 7
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract The role of genetic factors involved in the development of undifferentiated nasopharyngeal carcinoma (UNPC) in nonendemic areas has been poorly investigated. High-resolution human leukocyte antigen (HLA) class I genotyping carried out in 82 Italian UNPC patients and 286 bone marrow donors born in the same province showed that A*0201, B*1801, and B*3501, known to effi-ciently present Epstein-Barr virus (EBV)-derived epitopes, were significantly under-represented in UNPC patients. Moreover, the A*0201/B*1801 haplotype was significantly less frequent in UNPC cases, with a 90% reduced risk (odds ratio [OR] 0.1, 95% confi-dence interval [CI] = 0.0-0.5) to develop UNPC, suggesting an additive effect. Notably, all 5 BARF1 epitopes and 7 of the 8 LMP-2 epitopes known to bind A*0201 showed a fully conserved sequence in all the 31 Italian EBV isolates investigated. The 4 amino acid changes affecting the 436-447 LMP-2 epitope do not reduce, but rather increase in two cases, the predicted ability of "variant" epitopes to bind the HLA-A*0201 allele, as shown by immunoinformatic analysis. Moreover, a significantly increased risk for UNPC was associated with A*2601 (OR 2.4, 95% CI = 1.1-4.9) and B*4101 (OR 9.2, 95% CI = 2.5-34.3). These findings indicate that Italian UNPC patients have a distinct HLA-A and -B genotypic profile and suggest that the decreased risk for UNPC conferred by definite HLA class I molecules is probably related to their ability to efficiently present LMP-2 and BARF1 epitopes that are highly conserved in EBV isolates from this geographic region. These results have practical implications for the immunotherapy of UNPC.
Keyword BARF1
Epstein-Barr virus
HLA
LMP2
Nasopharyngeal carcinoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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