Molecular epidemiology of Epstein-Barr virus (EBV) in EBV-related malignancies

Sidagis, Jorge; Ueno, Kazuyoshi; Tokunaga, Masayoshi; Ohyama, Masaru; Eizuru, Yoshito

doi:10.1002/(sici)1097-0215(19970703)72:1<72::aid-ijc11>3.0.co;2-c

Cited by 46 publications

(40 citation statements)

References 27 publications

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“…Thus, the EBV in case 13 was type B, f variant and wild type LMP-1. The present results for EBV genotype and BamHIF RFLP are in line with the predominance of type A and the low f variant incidence previously reported for Japan [4,17].…”

Section: Figsupporting

confidence: 92%

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The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas

et al. 1999

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Five hundred and thirteen cases of gastric carcinoma were investigated for the presence of viral RNA, and the clinico-pathological data, geno-type, BamHIF restriction fragment polymorphism (RFLP) and specific LMP-1 30 bp gene deletion were also examined. EBVs detected in lymphocytes in 20 normal gastric mucosa, 7 lymphoma cell lines (LCLs) maintained in severe combined immunodeficiency (SCID) mice and 18 non-Hodgkin's lymphomas were compared with those in the gastric carcinoma cases. Thirty-three cases (6.4%) were demonstrated to be positive for EBV by means of EBER-1 RNA in situ hybridization. Clinico-pathological data showed no statistically significant difference in histological grading, location of cancer and status of vessel and lymphatic invasion between the EBV-positive and -negative groups, although the former significantly predominated in the submucosal invasion group (submucosal vs mucosal P=0.021; submucosal vs advanced cancer P=0.033). Some of these data were different from corresponding data in earlier reports. In cases that were evaluated by molecular biology, type A, wild-type F and LMP-1 gene deletion predominated except one in 21 informative cases, one in 24 and two in 16, respectively. EBVs detected in lymphocytes in normal gastric mucosa, LCLs in SCID mice and non-Hodgkin's lymphoma were also predominantly affected by type A, wild-type F and LMP-1 gene deletion with few exceptions. The results indicate a lack of genetic differences among EBVs in gastric carcinoma, normal population, LCLs of SCID mice and non-Hodgkin lymphomas. Some EBV infections in gastric carcinomas may be transient, especially in the submucosal invasion group.

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Section: Figsupporting

confidence: 92%

“…Results of the normal population are similar to those given in other reports from Japan [4,17]. It might be suggested that the majority of EBVs in the normal population in Japan are type A and wild type F and have LMP-1 deletion, reflecting the results of LCLs in SCID mouse and non-Hodgkin lymphomas.…”

Section: Figsupporting

confidence: 85%

The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas

et al. 1999

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“…The incidence of type B virus infection in Okinawa (34.1%) was nearer to that seen in Taiwan (16.7%) than to that seen in mainland Japan and southern China, but was still about twice as high as that seen in Taiwan. However, the incidence of the "f " variant in mainland Japan has been reported to be very low (1.4%), 24 and is similar to that seen in Okinawa. In our present study, the EBNA2 gene of the type A virus in Okinawa had non-silent mutations (sequence variations) at positions 48991 and 49173.…”

Section: Discussionmentioning

confidence: 63%

Epstein-Barr virus (EBV) subtype in EBV related oral squamous cell carcinoma in Okinawa, a subtropical island in southern Japan, compared with Kitakyushu and Kumamoto in mainland Japan

Higa

Kinjo

Kamiyama

et al. 2002

Journal of Clinical Pathology

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Aim: In Okinawa, a subtropical island located between the East China Sea and Pacific Ocean, 2000 km south of mainland Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that seen in mainland Japan, and a large number of these patients have been reported to be infected with the Epstein-Barr virus (EBV). This study aimed to gain a better understanding of the pathogenesis of this malignancy in this area by carrying out genomic analysis of EBV. Methods: Fifty four patients with oral squamous cell carcinoma reported from 1997 to 1999 in Okinawa were compared with 21 and 20 patients from Kitakyushu and Kumamoto in Kyushu, mainland Japan, respectively. Diagnosis was confirmed by conventional histological examination of paraffin wax sections. EBV was detected by non-isotopic in situ hybridisation (NISH) and the polymerase chain reaction (PCR) (Bam HI-F, EBV nuclear antigen 2 (EBNA2), and latent membrane protein 1 (LMP-1) regions). Sequence analysis of the PCR products was also carried out. Results: In Okinawa, 25 patients were found to be infected with EBV type A by analysing the 3′ sequence divergence of the EBNA2 genes. Six patients were positive for EBV type B, and eight for both type A and B. Therefore, type A virus infection was demonstrated in 33 of 54 patients, and type B in 14 of 54. In total, 39 of 54 patients were infected with EBV. However, the "f" variant was shown in only one patient, who was also infected with type A virus. In contrast, 97.0% of EBV type A infected patients showed a 30 bp deletion of the LMP-1 gene, but those infected with EBV type B did not. Sequence analysis of the type A virus EBNA2 gene revealed slight variations of the sequence (mutations)-48991 G→T and 48998 C→A-in 18 of 33 cases compared with the B95-8 strain, and in 14 cases, in addition to these, a further mutation of 48917 T→C was demonstrated; in the single remaining case, only one mutation at 49137 A→G was detected. The mutations at 48991 (G→T), and 49137 (A→G) are associated with amino acid changes Arg→Met and Thr→Ala, respectively. In contrast, no mutation was seen in the EBNA2 DNA from the 14 cases of type B virus when compared with that of the Jijoye strain. In Kitakyushu and Kumamoto, only 10 of 41 patients (six in Kitakyushu and four in Kumamoto) were infected with EBV. Among them, nine patients were infected with type A virus, and only one patient from Kitakyushu was infected with type B virus. The 48991 G→T and 48998 C→A mutations of the EBNA2 region were demonstrated in type A virus, but the 48917 T→C and 49137 A→G mutations were not when compared with the B95-8 strain. In the case of type B virus no mutation was noted. A 30 bp deletion was found in these nine cases of type A, but not in type B. The sequence analysis of EBV type A in Okinawa, Kitakyushu, and Kumamoto showed slight variations when compared with B95-8, but EBV type B LMP-1 did not when compared with the Jijoye strains. Conclusion: In Okinawa, EBV infection was frequently demonstrated in oral squamous cell carcinoma (p < 0.001)....

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“…The association of EBV with malignant lymphoma (1) and carcinoma (2,3) of the stomach is well documented, but gastrointestinal lesions have rarely been observed as a complication of IM. EBV gastritis is rarely recognized, and to our knowledge, only 4 cases have previously been reported (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Gastritis Associated with Epstein-Barr Virus Infection

et al. 2010

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Infectious mononucleosis is a self-limiting clinical syndrome caused by primary Epstein-Barr virus (EBV) infection. EBV-associated gastritis, however, has rarely been documented. We report a case of a 17-year-old woman who presented with fever, sore throat, and epigastric pain. Upper endoscopy revealed diffuse granular mucosae and elevated lesions in the stomach. Histologically, the biopsied mucosa was infiltrated by numerous atypical lymphocytes. From clinical, histopathologic, immunohistochemical, and in situ hybridization analyses, we diagnosed EBV-associated gastritis. Her symptoms spontaneously resolved, and follow-up endoscopy revealed improvement and no atypical lymphocytes. To prevent misdiagnosis and unnecessary treatment, the possibility of EBV-associated gastritis should be considered.

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Molecular epidemiology of Epstein-Barr virus (EBV) in EBV-related malignancies

Cited by 46 publications

References 27 publications

The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas

The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas

Epstein-Barr virus (EBV) subtype in EBV related oral squamous cell carcinoma in Okinawa, a subtropical island in southern Japan, compared with Kitakyushu and Kumamoto in mainland Japan

Gastritis Associated with Epstein-Barr Virus Infection

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