Prevalence of mutations and 30-bp deletion in the C-terminal region of Epstein-Barr virus latent membrane protein-1 oncogene in reactive lymphoid tissue and non-nasopharyngeal EBV-associated carcinomas in Hong Kong Chinese.

A specific variant of Epstein-Barr virus (EBV) with a 30-bp deletion in the C-terminal region of the LMP1 gene has been found in some EBV-associated malignancies. To better understand the tumorigenic role of this LMP1 variant, we used PCR and sequencing to examine the LMP1 gene in 38 EBV-associated carcinomas (EBV-CAs) occurring in various organs (6 lung, 10 salivary gland, 5 sino-nasal, 16 gastric and 1 metastatic NPC), 55 reactive lymphoid tissues from tonsils (TON) and 67 EBV-negative tumours in various organs (22 adenolymphoma of salivary gland, 14 gastric and 31 colonic adenocarcinomas), where the virus was demonstrated in lymphocytes. The TON showed prevalence of both deleted and non-deleted variants of LMP1, with dual infection being common. Significantly more of the LMP1 variant was deleted in EBV-CA and in EBV-negative tumours. Sequencing showed that the deleted and non-deleted variants have different sets of amino acid mutation. Mutations in codon 344 and 355 in the non-deleted variant disrupted the 9 nucleotide repeat flanking the deletion and thus may have conferred resistance to the deletion. The prevalence of both variants in the TON, with enrichment for the deleted variant in various organs, argues for the existence of an immune selection pressure in our population. The deleted variant, which may have a higher tumorigenic potential, may contribute to the high incidence of NPC, as well as the occurrence of EBV-CA in organs outside the nasopharynx in our locality.