Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.


METHODS
In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffin-embedded tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme.


RESULTS
LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in non-malignant tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma samples but not in NPC tissues. The loss of XhoI restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour XhoI-loss variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). XhoI-loss was found in 19/19 Chinese versus 14/19 Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; XhoI-loss, p = 0.046) and histological type of NPC (30-bp deletion, p = 0.011; XhoI-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%) and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of XhoI restriction site. A significant relationship was found with the Chinese race but not histological type.


CONCLUSIONS
The incidence rate of 56% for LMP1 30-bp deletion was lower compared to previously reported rates of 75-100% in NPC tissues. Coexistence of variants with and without 30-bp deletion was found only in 5/29 plasma samples. The incidence rate of XhoI restriction site loss in NPC was comparable to other studies from endemic regions such as Southern China. For the first time, the presence of LMP1 30-bp deletion or XhoI-loss was associated with the Chinese race and type III NPC. Both these variants were not found in non-malignant tissues. The influence of these variants on disease progression and outcome in Chinese and type III NPC requires further investigation.
See
Hui Shien
HS
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia. shuishien@yahoo.com
Yap
Yoke Yeow
YY
Yip
Wai Kien
WK
Seow
Heng Fong
HF
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D001665:Binding Sites; D002681:China / Q000208:ethnology; D003598:Cytoskeletal Proteins; D004279:DNA, Viral; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D010865:Pilot Projects; D014763:Viral Matrix Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D014763:Viral Matrix Proteins; D015252:Deoxyribonucleases, Type II Site-Specific