Frequent allelic loss at the FRA3B site in endemic nasopharyngeal carcinoma: association with clinical features and Epstein-Barr virus infection.

In this study, we aimed to precisely define the patterns of allelic loss at the FRA3B site in endemic nasopharyngeal carcinoma and to determine whether an association exists between allelic loss, clinicopathological features and Epstein-Barr virus infection. We examined the loss of heterozygosity in 40 cases of nasopharyngeal carcinoma from an endemic area in southern China, using eight high dense, polymorphic, microsatellite markers within or flanking the FRA3B site. Loss of heterozygosity at the FRA3B region was shown in 31 (77.5 per cent) primary tumours. Loss of heterozygosity was found most frequently at the D3S1300 (55.6 per cent) and D3S2757 (50.0 per cent) loci. The common area of deletion was located between the D3S4103 and D3S4260 loci. In nasopharyngeal carcinoma, loss of heterozygosity at the FRA3B/fragile histidine triad locus correlated with the following clinicopathological parameters: tumour T-stage, lymph node status, clinical stage, tumour differentiation and serum antibody titres of immunoglobulin (Ig) A against Epstein-Barr virus capsid antigen. Significantly frequent loss of heterozygosity was observed in nasopharyngeal carcinoma with tumour stages T3 and T4, lymph node metastasis and advanced tumour-node-metastasis staging (III and IV). Very frequent loss of heterozygosity was also observed to correlate with World Health Organization type III nasopharyngeal carcinoma histopathology. We also found that nasopharyngeal carcinoma patients with high titres of IgA against Epstein-Barr virus capsid antigen showed very frequent loss of heterozygosity. Allelic loss at the FRA3B site occurs significantly more commonly in endemic nasopharyngeal carcinoma patients. This suggests that the region between D3S4103 and D3S4260 may represent a preferential molecular target in nasopharyngeal carcinogenesis.