The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

[Incidence of oral hairy leukoplakia in human immunodeficiency virus-seropositive adult patients in Yunnan, China].

OBJECTIVE: To study the incidence rates, clinical characteristics of oral hairy leukoplakia (OHL) and its relation to the immune status in a sample of human immunodeficiency virus (HIV)-infected adults in Yunan, China. METHODS: 1 060 adult patients with HIV from January 2008 to June 2010 were evaluated. The age, gender, education grade, diagnosis time of HIV-infected, route of transmission, xerostomia, oral candidiasis, high active antiretroviral therapy and CD4 lymphocytes counts. The occurrence of OHL was recorded by oral examination. The relationship of CD4 lymphocytes counts and the incidence of OHL were analyzed by statistical methods. RESULTS: There were 94 OHL patients in 1 060 HIV patients (8.9%). The average age of the OHL patients was (39.33 +/- 10.45) years old. 90% OHL was found on the two lateral aspect of the tongue. The CD4 lymphocytes of 70.2% OHL patients were less than 200 mm-3. CONCLUSION: OHL is a frequent finding in patients with indicates severe immunosuppression and associated with the reduction of CD4 lymphocytes.