Prevalence of LMP1 deletion variant of Epstein-Barr virus in nasopharyngeal carcinoma and gastric tumors in Hong Kong

Abstract

Prevalence of LMPl deletion variant of Epstein-Barr virus in nasopharyngeal carcinoma and gastric tumors in Hong KongChang et al. (1995) have described a prevalent strain of Epstein-Burr virus (EBV) associated with T-cell lymphoma and nasopha yngeal carcinoma (NPC) in the Taiwanesepopulation. The strain was identical to a previously reported NPC-EBV strain from a cell line -1510 originating from Taiwan, which showed Xho I restriction enzyme polymorphism in exon 1 and a 30-bp deletion in exon 3 of the latent membrane protein 1 (LMP1) gene (Chang et al., 1995Chen et al., 1992.We have also identified a prevalent EBV strain (HKNPC-EBV) in nasopharyngeal carcinoma in Hong Kong, where the incidence of this cancer is high. The sequence of the LMPl gene of this prevalent strain is basically similar to that reported by Chang et al. (1995) but with some specijic differences.We examined 74 NPC primary biopsies from Southern Chinese patients in Hong Kong and 3 NPC xenograjis (HK-2117 HK-666 and HK-1915) by PCR-RFLP analysis, and observed loss of the Xho I site in exon I of the LMPl gene in all NPC biopsies and xenograjis. A 30-bp deletion at the C-termind region was also identified in 69/ 74 (93%) biopsies and 313 (100%) xenografts. Upon SSCP and direct DNA sequencing analysis, a prevalent strain with a specific sequence of the LMPl gene was observed in 64174 (86%) biopsies and 213 xenograjis (HK-2117 and HK-666). This sequence was characterized by a 30-bp deletion at codons 346 to 355 (nt 168285 to 168256), and a unique G to A mutation at codon 335 (nt 168317, GGC to GAC), resulting in a change of amino acid from glycine to aspartic acid. The 30-bp deletion site was similar to that reported for the NPC-CAO strain which had a Northern Chinese origin (Hu et al., 1991), but differs from that of the Taiwanese strain with deletion site at nt 168282 to 168253 reported by Chang et al. (1995). Otherwise, mutations at codon 322 (CAA t o w ) , 334 (CAG to CGG), 338 (TTG to TCG) and 342 (GGA to GGT) were identical to those seen in the Taiwanese strain. The mutational change at codon 335, however, has not been reported previously in either the NPC-CAO strain from Northern China or NPC-1510 strain from Taiwan.Furthermore, 2 other minor EBVstrains (I and II) were also identijied in our NPC biopsies. The first of these minor strains (I), found in 5174 (7%) biopsies and one xenograft (HK-1915), did not have the afore-mentioned base substitution at codon 335, although the 30-bp deletion and codon changes in the C-terminus of the LMPl gene were otherwise the same as in the prevalent gpe. The second minor strain (II), found in 5/74 (7%) NPC biopsies, did not have the 30-bp deletion at the C-terminus, although loss of the Xho I site at the N-ter-minus was found in all these cases. This minor strain II also consistently exhibited base substitutions at codon 331, 338, 342,344 and 355. To determine whether the prevalent EBV strain in our NPC biopsies could be found in other EBV-related tumors in Hong Kong, we also investigated tumor tissue...

Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Upregulates Glucose Transporter 1 Transcription via the mTORC1/NF-κB Signaling Pathways

“…However, the different strains of LMP1 and experimental approaches used in the two studies may also be accountable for the discrepancy observed in the action of LMP1 on Glut-1 transcription. In our study, the 2117-LMP1 used is the common LMP1 variant detected in nasopharyngeal carcinoma (NPC) from Hong Kong patients (33). The 2117-LMP1 was reported to have more potent activity in NF-B activation but lower cellular toxicity than the B95.8-derived LMP1 sequences commonly used in B cell lymphoma studies (34).…”

Genomic Sequence Analysis of Epstein-Barr Virus Strain GD1 from a Nasopharyngeal Carcinoma Patient

“…Most LMP1 genes derived from Chinese NPC biopsy specimens are marked by the 30-bp deletion (nt 168266 to 168295) in the carboxyl terminus, a loss of the XhoI site in the amino terminus, and multiple base substitutions in the coding region (9,10,22,25). Although the 30-bp deletion in LMP1 was detected in 100% of 48 NPC biopsy specimens in Taiwan (8), in 34 of 37 NPC biopsy specimens in Hong Kong (11), and in 16 of 21 NPC biopsy specimens in Guangxi and Shanghai (51), Zhang et al (56) reported that the 30-bp deletion in LMP1 represents a geographical-or race-associated polymorphism rather than an NPC disease phenotype-associated polymorphism. Recently, the consistent sequence variation in LMP1 has been used to distinguish the various EBV strains, which were termed strains China 1, China 2, Med, China3, Alaskan, NC, and B95.8.…”

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

“…The 30-bp deletion, detected also in a proportion of Alaska native, Caucasian (125,126), Malaysian (122), and North African NPC (127,128), seems to enhance the transforming potential of LMP1 in vitro, and may be present in more aggressive disease forms (117,(129)(130)(131). However, there is no strong evidence that the deleted variant is associated with increased risk of NPC (120,123,132,133), and there is a lack of large, well-designed epidemiologic studies of risk associations with EBV variants. Furthermore, the detection of specific LMP1 mutations in NPC tumors from diverse regions suggests that EBV strain variation is not geographically correlated with NPC incidence.…”