Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas.
It is still unknown what kinds of roles Epstein-Barr virus (EBV) infection that are highly specific to salivary gland lymphoepithelial carcinomas (LECs) play in their tumorigenesis. To clarify the significance of EBV in LECs, we paid particular attention to the LMP1 gene, which is responsible for triggering several pathways for activating transcription factors. Sixty-one cases of EBV positive LECs confirmed by PCR and in-situ hybridization were collected from various areas of the world and studied immunohistochemically for latent membrane protein-1. Furthermore, PCR for the LMP1 carboxyl (C)-terminus region was performed, and the PCR products were sequenced for detection of other mutational events. LMP1 gene products were immunohistochemically demonstrated in 51% of the cases, while PCR amplification of the LMP1 gene was successful in 41 cases (67%). Among them, a 30 bp deletion in the C-terminus of the LMP1 gene, which had been shown to be characteristic to EBV in Chinese nasopharyngeal carcinomas, was found in 20 cases (32%). Most of them were from Guangzhou, Chengdu and Taiwan, while most of the cases from Shanghai and other areas exhibited no 30 bp deletion. In addition, several point mutations including codon 338 of LMP1 were commonly shared by the cases with or without the 30 bp deletion. These results indicate that there are 2 major genomic variations of EBV infecting salivary gland LECs. The frequent mutational events in the C-terminus in addition to the 30 bp deletion also seem to be critical for the pathogenesis because such mutational events may possibly promote cellular proliferation.
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan.
Kai Yu
KY
Jen
Jun
J
Cheng
Jian
J
Li
Lanyan
L
Wu
Yingfang
Y
Li
Shifeng
S
Yu
Hanliang
H
Lin
Zhilong
Z
Chen
Vladimir
V
Gurtsevitch
Takashi
T
Saku
D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000821:virology*; D002681:China / Q000453:epidemiology; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D005814:Genes, Viral; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012426:Russia / Q000453:epidemiology; D012468:Salivary Gland Neoplasms / Q000208:ethnology / Q000821:virology*; D017384:Sequence Deletion; D013624:Taiwan / Q000453:epidemiology; D014412:Tumor Virus Infections / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics
D003062:Codon; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins