以往研究提示，c-myc和c-erbB-2癌基因在鼻咽癌中过表达。为了阐明这两种癌基因过表达的分子机制，应用当前肿瘤研究新技术——组织微阵列，结合间期双色荧光原位杂交(FISH)和免疫组化(IHC)，对267例鼻咽癌组织、24例癌旁组织和29例鼻咽部慢性炎症组织进行了大样本研究。结果发现，号咽癌c-myc和c-erbB-2癌蛋白过表达发生率分别为48%￥～63%和20%～38%；但c-myc和c-erbB-2两个癌基因在鼻咽癌中均无扩增；8与17号着丝粒探针杂交则分别显示有43%～50%和20%～27%的鼻咽癌染色体呈现多体性。蛋白表达分析表明，c-erbB-2表达与17号染色体多体性有关（P<0.0005）。

Nasopharyngeal carcinoma (NPC) has a striking geographical and ethnical distribution. It occurs with high frequency in southern China and Southeast Asia. Family clustering was also observed in NPC and a typical family with 15 NPC cases was introduced in this paper. Epidemiological and genetic studies have been carried out in the previous decades and vast information was accumulated for familiar NPC, in terms of risk factors, inheritance mode, and involvement of gene polymorphisms. The major findings in this field were summarized. Furthermore, future directions leading to understanding the genetic mechanism of the familial form of NPC was also discussed.

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk1-6. Although the HLA-Bw46 locus is associated with increased risk of NPC7,8, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (Iod) score of 3.06 and a heterogeneity-adjusted Iod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives Iod scores of 3.54 at D4S405 (P=5.4

carcinomas (NPC) were examined by a lleIotype analysis for the ptuposes of detecting potential association between loss of heterozygosity (LOH), clinicopathological parameters and Epstein-Barr virus (EBV) infection. LOH was performed using 257 polymorphic markers on 22 chromosomes. High frequency LOH (≥60%) was observed on 12 chromosome arms including 1p, 2p, 2q, 3p, 3q, 5q, 9p, 9q, 1 lq, 13q, 14q and 17q, with the highest LOH frequency of 91% on 3p. Seventy-three loci presented LOH frequency≥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, 14ql3-q11, 14q32 and 19q13. On 1p36-p34, 2p25-p24, 5qI3-q11, 5q31-q33 and 19q13 are reported for the first time. LOH was correlated with specific clinicopathological parameters including tumor T-stage, N-stage, TNM-stage, tumor differentiation and serum antibody titers of IgA against vires capsid antigens (VCA) and early antigen (EA) of EBVin NPC (LOH frequency≥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 observed on 12p11 (65%) in NPC with stage T1+T2. Significantly higher LOH frequency 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 IgA/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 NPC patients with high titers of IgA/VCA and IgA/EA showed high LOH frequency on 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