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 i n the C-terminal region of the LMP1 gene has been found in some EBV-as sociated malignancies. To better understand the tumorigenic role of th is LMP1 variant, we used PCR and sequencing to examine the LMP1 gene i n 38 EBV-associated carcinomas (EBV-CAs) occurring in various organs ( 6 lung, 10 salivary gland, 5 sine-nasal, 16 gastric and I metastatic N PC), 55 reactive lymphoid tissues from tonsils (TON) and 67 EBV-negati ve tumours in various organs (22 adenolymphoma of salivary gland, 14 g astric and 31 colonic adenocarcinomas), where the virus was demonstrat ed in lymphocytes, The TON showed prevalence of both deleted and non-d eleted variants of LMP1, with dual infection being common, Significant ly more of the LMP1 variant was deleted in EBV-CA and in EBV-negative tumours, Sequencing showed that the deleted and non-deleted variants h ave different sets of amino acid mutation, Mutations in codon 344 and 355 in the non-deleted variant disrupted the 9 nucleotide repeat flank ing the deletion and thus may have conferred resistance to the deletio n, The prevalence of both variants in the TON, with enrichment for the deleted variant in various organs, argues for the existence of an imm une selection pressure in our population, The deleted variant, which m ay have a higher tumorigenic potential, may contribute to the high inc idence of NPC, as well as the occurrence of EBV-CA in organs outside t he nasopharynx in our locality. (C) 1997 Wiley-Liss, Inc.