Nonrandom allelic loss on chromosome 3p is a common event in nasopharyngeal carcinoma (NPC) with the implication that certain tumor suppressor gene(s) in this region are involved in the pathogenesis of these tumors, The BLU gene, located at 3p21.3, has recently been identified as a candidate tumor suppressor gene due to the occurrence of missense mutations and loss of its expression in lung cancer. To investigate the involvement of BLU gene in NPC, we examined tumors and cell lines. No pathogenic mutations were detected in the entire coding region of this gene in 45 primary NPC tumors and 5 NPC cell lines. While BLU was expressed in 100% (15 of 15) of noncancerous nasopharyngeal epithelia, its transcripts were missing in all 5 NPC cell lines, and absent or reduced mRNA levels were observed in 78% (2B of 36) of the primary tumors. In the NPC cell lines, loss of BLU expromoter sequence, and expression was restored after treatment with 5-aza-2-deoxycytidine. Methylation specific PCR analysis revealed that the BLU promoter was highly methylated in 74% (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9 non-neoplastic nasophamoter region. The high incldence of BLU alterations suggests that it may be one of the critical tumor suppressor genes on chromosome 3p21.3 involved in the development of NPC.

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

To identify genetic alterations associated with the development and progression of human nasopharyngeal carcinoma (NPC), 57 tumors were analyzed by comparative genomic hybridization (CGH). In 47 cases, chromosomal imbalances were found. Several recurrent chromosomal abnormalities were identified in the present study. The most frequently detected chromosomal gains involved chromosome arms 12q (24 cases, 51%), 4q (17 cases, 36%), 3q (16 cases, 34%), 1q (15 cases, 32%), and 18q (15 cases, 32%). Common regions of gain involved 12q13-q15, 4q12-q21, and 3q21-q26. High-copy-number increases of chromosomal materials were detected in four chromosomal regions, 3q21-q26.2, 4p12-q21, 8p, and 12q14-q15. The most frequently detected loss of chromosomal materials involved chromosome arms 16q (26 cases, 55%), 14q (21 cases, 45%), 1p (20 cases, 43%), 3p (20 cases, 43%), 16p (19 cases, 40%), llq (17 cases, 36%), and 19p (16 cases, 34%). The most common regions of loss involved 14q24-qter, 1pter-p36.1, 3p22-p21.3, 11q21-qter, and the distal region of 19p. Genomic alterations detected by CGH were compared and found to be largely consistent with those identified in banding analysis and loss of heterozygosity studies. However, several previously unrecognized recurrent alterations were also identified in the present study, including gain of 4q and 18q, and loss of 16q, 14q, and 19p. In addition, gain of lq, 8q, 18q, and loss of 9q showed a statistically significant association with advanced clinical stages (P<0.05). Identification of recurrent sites of chromosomal gain and loss identify regions of the genome that may contain oncogenes or tumor suppressor genes, respectively, which may be involved in the tumorigenesis of NPC. Published 2000 Wiley-Liss, Inc.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China, especially in the Guangdong area. To demonstrate a comprehensive profile of loss of heterozygosity (LOH) in NPC, we applied a large panel of 382 microsatellite polymorphism markers covering all the 22 autosomes in 98 cases of sporadic primary NPC. Of the 335 informative markers, 83 loci showed high level of LOH (presence in equal to or more than 30% cases) and most of the high frequent loci were clustered to chromosome 1p36 and 1p34, 3p14-p21, 3p24-p26, 3q25-q26 and 3q27, 4q31 and 4q35, 5q15-21 and 5q32-q33, 8p22-p23, 9p21-p23 and 9q33-q34, llp12-p14, 13q14-q13 and 13q 31-q32, 14q13-q11, 14q24-q23 and 14q32. High frequency of LOH was found in chromosomes 3, 5, 9 and 11 (≥50%), while medium frequency of LOH was found in chromosomes 1, 4, 6, 14, 17 and 19 (40-49%). Several new regions showing high frequency of LOH were found in chromosome 1p36, 3q25-q26, 3q27, 5q15-q21, 8p22-p23 and 11p12-14. The relationship between LOH and TNM stage of NPC was evaluated. Regions 6p23 (D6S289), 8p23.1 (D8S549) and 9q34.2 (D9S1826) showed higher frequency of LOH in later stages (Ⅲ and Ⅳ) than in earlier stages (Ⅰ and Ⅱ) (P<0.05). Thus, our study provides a global view on allelic loss in the development of NPC and should shed light on the way for localization of putative tumor suppressor genes associated with the pathogenesis of NPC.

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）。