Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma

Sixty-one human nasopharyngeal carcinomas (NPC) were examined by allelotype analysis for the purposes of detecting potential association between loss of heterozygosity (LOH), clinicopathological parameters and Epstein-Barr vi rus (EBV) infection. LOH was performed using 257 polymorphic markets on 22 chromosomes, High frequency LOH (greater than or equal to 60%) was observed on 12 chromosome arms including 1p, 2p, 2q, 3p, 3q, 5q, 9p, 9q, 1 1q, 13q, 14q and 17q, with the highest LOH frequency of 91% on 3p. Seventy-three lo ci presented LOH frequency greater than or equal to 30%; most of these loci clustered on 1p36 p34, 2p25-p24, _3p14-p21, 3p24-p26, 5q11-q14, 5q31-q33, 9p21-p23, 9q33-q34, 11q23-q25, 13q12 q14, 13q31-q33, 14q13-q11, 14q32 and 1 9q13. On 1p36-p34, 2p25-p24, 5q13-q11, 5q31-q33 and 19q13 are reported for the first time. LOH was correlated with specific clinicopathological parame ters including tumor T-stage, N-stage, TNM-stage, tumor differentiation and serum antibody titers of IgA against vints capsid antigens (VCA) and early antigen (EA) of EBV in NPC (LOH frequency greater than or equal to 30 %). Significantly high LOH frequency was observed on 9p21 (56%) and 19q13 (50%) in NPC with stage T3+T4, while significantly, higher LOH frequency was obs erved on 12p11 (65%) in NPC with stage T1+T2. Significantly higher LOH freq uency, on 19q13 was also observed in NPC with advanced TNM-stage (III+IV). High fractional allelic loss (FAL) value and high antibody titers of EBV Ig A/VCA and/or IgA/EA were significantly correlated with T3+T4-stage, distant lymph node metastasis and advanced TNM-stage of NPC. We also found that NP C patients with high titers of IgA/VCA and IgA/EA showed high LOH frequency oil 16q (48%) and 19q13 (48%). These results suggest that LOH on 9p21, 16q and 19q13 may be responsible for the aggressiveness and progression of NPC ; there may be an interaction between allelic loss and EBV infection in the etiology of NPC. High frequency of LOH on 4q21 and 14q11-q12 were also fou nd to be correlated with WHO type III NPC histopathology, suggesting that L OH on these regions may cause poor NPC differentiation. Our data also may b e useful for the development of a NPC molecular staging system, a system wh ich may augment the use of clinical pathological features in the diagnosis and prognosis of this disease.