Exploration of multigene, multistep and multi-pathway models of nasopharyngeal and colorectal carcinogenesis

Objective To construct tree models for nasopharyngeal carcinoma (MPC) and colorectal carcinoma (CC) and explore the oncogeneic process of NPC and CC. Methods Based on the software that Desper et al. developed, tree models were constructed for CC from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively. Results Tree models for CC suggested that loss of 18q and gain of 20q were important early events in colorectal carcinogenesis. As changes in - 18q occurred prior to those in —17p, a cause-effect relationship might exist between them. Tree models for NPC suggested that loss of 3p was an important early event in nasopharyngeal carcinogenesis, and deletion of 11q. 14q. 16q and 9p were also nonrandom genetic events in carcinogenesis. suggesting that there might be tumor -associated genes existing on these chromosome arms. The tree model also indicated the existence of oncogenes on the short arm of chromosome 12. Conclusion Constructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and muitipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis. This work was supported by the grant from the Ministry of Science and Technology Key Basis Research Program(973) (Grant. 1998051201)     

鼻咽癌和结直肠癌多基因多阶段多途径模型的探讨

目的 构建鼻咽癌和结直肠癌树模型,探讨和比较两种癌癌变过程中多基因、多阶段、多途径的发生发展模式。方法 根据118例结直肠癌和140例中国南方鼻咽癌比较基因组杂交的数据,利用Desper等建立的软件,分别构建结直肠癌和鼻咽癌的树模型。结果 结直肠癌树模型提示,-18q和 20q可能是结直肠癌变中的重要早期事件,并且-18q先于-17p出现,两者之间可能存在因果关系。鼻咽癌树模型提示,-3p是重要的早期事件,-11q、-14q、-16q、-9p亦是鼻咽癌发生中的非随机事件,这些染色体臂上可能存在着与鼻咽癌密切相关的肿瘤相关基因;同时树模型还提示,12p上可能也有与鼻咽癌相关的瘤基因。结论 根据比较基因组杂交资料构建的肿瘤发生发展的树模型,可以揭示肿瘤多基因、多阶段、多途径发生发展的模式。     

鼻咽癌分子遗传学研究进展

探讨鼻咽癌（nasopharyngeal carcinoma,NPC）发生发展的分子遗传学事件及其变异的NPC临床病理变化的影响。对原发性NPC进行杂合性缺失（loss of hetrozygosity,LOH)和比较基因组杂交（comparative genomic hybridization CGH)分析,观察到NPC发生高频率LOH的染色体主要位于1p、3p、9p、9q、11q、13q、14q、16q和19p,并定位了相应的LOH最小丢失区,并发现特定区域LOH与鼻咽癌临床病理有密切关系;LOH最化值高（FAL值）并伴随病人血清高滴度EBV／EA和EBV／VCA抗体的NPC,多表现为T3＋F4期、进展期TNM／Ⅲ Ⅳ期和远处淋巴结转移。NPC发生遗传物质扩增（gain）的染色体主要位于1q、2q、3q、6p、6q、7q、11.2、8q、11q13、12、15q、17q和20q,表明在这些区域可能存在与NPC发生发展相关的癌基因（oncogenes）活化,且1q,8q,18q的坟增和9p的丢失与晚期NPC有密切关系。正常鼻咽上皮和鼻咽上皮不典型生病变,3p区LOH的检出率分别高达74％和75％,表明3p区缺失是NPC发生过程中极早期分子事件。连锁分析表明HLA基因和细胞色素P4502E1酶基因可能是NPC的遗传易感基因,并定位了新的潜在NPC易感基因位点。应用cDNA微阵列技术,发现细胞周期蛋白、抗凋亡因子、某些癌基因／肿瘤抑制基因、生长促进因子、肿瘤发生生长因子和肿瘤血管生长因子等在NPC发生上调控表达;不同临床分析的NPC与正常鼻咽上皮间均存在差异表达。NPC发生遗传不稳定性（缺失和扩增）是常见的分子事件,遗传变异在NPC的发生、发展过程中起重要作用。通过LOH、CGH、连锁分析和微阵列分析确定NPC特异的分子标记物,能提供用于NPC早期诊断和预后判断的分子标记物,并将使我们建立独立于传统临床分期和分型的新的NPC分子分期的分子分型成为可能。     

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase

Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappaB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development.     

原发性鼻咽癌中高频率的4q增多和1p丢失

目的 阐明中国广东籍患者原发性鼻咽癌（NPC）的遗传学变化。方法 用比较基因组杂交技术（CGH）检测17例原发性NPC遗传物质的增多和丢失情况。结果 在半数以上患者中发现4q增多和1q丢失,其他较为常见的染色体变化是12q、1q、2q、3q和8q增多。以及3q、11q、14q、15q、13q、Xq、9q、10q、10q和16q丢失。结论 广东原发性NPC的遗传学改变为4q、12q和1q增多以及1q、3q、11q和14q丢失,这些区域可能含有与NPC发病有关的癌基因与抑癌基因。     

DNA copy profile in nasopharyngeal carcinoma and its correlation with clinical staging

Nasopharyngeal carcinoma (NPC) represents a major public health problem in Southern China. Aetiological studies suggest that the development of NPC is due to a complex interaction of genetic factors, dietary exposure to chemical carcinogens and EBV infection[1]. The molecular events leading to the development of NPC have yet to be elucidated. Due to the poor quality of metaphases and low mitotic index in cultures established from primary tumors, very few primary NPC cytogenetic analyses…     

染色体3p14.2区域一个与鼻咽癌呈负相关EST的鉴定

目的：寻找染色体３Ｐ１４．２区域与鼻咽癌相关的表达序列标记,为筛选鼻咽癌候选基因打下基础。方法：运用生物信息学同生比较筛选ＥＳＴ的策略,结合Ｎｏｒｔｈｅｒｎ杂交和逆转录ＰＣＲ方法,检测３ｐ１４．２区域的相关ＥＳＴＳ在鼻咽癌和正常鼻咽组织中的表达。结果：在３Ｐ１４．２区域筛选到一个在鼻咽癌中低表达的ＥＳＴＷ２３３１２,与正常鼻咽上上以组织相比较,在鼻咽癌细胞株及１３例鼻咽癌活检组织中的５便其表达下调     

人鼻咽上皮细胞株HNE—1染色体高分辨显带的研究

作者首次采用高分辨染色体G显带技术,对本室建立的人鼻咽癌上皮细胞株“湖南一号”(HNE-1)进行了细胞遗传学研究。HNE-1细胞株在第15代时,染色体数目变异在68—78之间,众数为74。所检细胞均含有结构异常的染色体。出现频率比较高的标记染色体15条,其中某些标记染色体只有在高分辨染色体上才清楚地显示出结构重排。此外还发现少数细胞内存在双微体和核内复制。与其它鼻咽癌上皮细胞株比较,发现7号染色体部分缺失del(7)(q32)在CNE、HNE-1及鼻咽癌活检组织中同时存在,这一标记染色体可能与鼻咽癌的发生有重要联系。     

Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches

Nasopharyngeal carcinoma (NPC) is consistently associated with EBV infection and prevalence in southern China and Southeast Asia. In addition to EBV, the development of NPC involves cumulative genetic and epigenetic changes influenced by predisposing genetic factors and environmental carcinogens. Over the past two decades, knowledge of genetic and epigenetic alterations of NPC has rapidly accumulated. Multiple chromosomal abnormalities (e.g. copy number changes on chromosomes 3p, 9p, 11q, 12p, and 14q), gene alterations (e.g. p16 deletion and LTBR amplification), and epigenetic changes (e.g. RASSF1A and TSLC1 methylation) have been identified by various genome-wide approaches, such as allelotyping, CGH, and microarray analysis. In this review, we will discuss the critical genetic events that contribute to the initiation and progression of NPC. Studies on the precancerous lesions and in vitro immortalized nasopharyngeal epithelial cell models provide important evidence for the involvement of genetic alterations and EBV infection in early development of this cancer. A hypothetical model describing the role of EBV latent infection and multiple genetic changes in NPC tumorigenesis is proposed.     

鼻咽癌及癌前病变组织中p16蛋白表达的研究

目的观察p16蛋白在鼻咽癌组织中的表达状态,探讨其与鼻咽癌的发生、发展关系。方法应用S-P免疫组化法检测p16蛋白在50例鼻咽癌、20例鼻咽粘膜慢性炎组织中的表达。结果鼻咽癌p16蛋白表达率为24.0%,显著低于鼻咽粘膜慢性炎组(P<0.01)。角化性鳞癌p16蛋白的表达率明显高于分化型非角化性癌和未分化癌(P<0.05)。20例淋巴结转移阳性组中p16蛋白表达率显著低于14例阴性组(P<0.05)。结论p16蛋白的缺失可能涉及鼻咽癌的发生、发展过程,且与鼻咽癌的转移、组织学分型有关。     

人鼻咽癌顺铂耐药细胞系 (CNE2/DDP)及其亲代细胞 (CNE2)的比较基因组杂交研究

背景与目的：比较基因组杂交(comparative genomic hybridization,CGH)是一种在荧光原位杂交(FISH)技术上发展起来的,用于检测两个基因组间相对DNA拷贝数的改变(缺失或扩增),并将这些变化在染色体上进行定位的分子细胞遗传学方法。为全面了解鼻咽癌耐药细胞与药物敏感细胞在基因组DNA水平上可能存在的差异,以及这种差异在肿瘤耐药性产生中的意义,我们用CGH技术对鼻咽癌耐药细胞系(CNE2／DDP)和其亲代药物敏感细胞(CNE2)的基因组DNA进行检测和分析。方法：提取两种癌细胞及正常胎盘组织的基因组DNA,以随机引物法进行荧光标记(CNE2／DDP和CNE2 DNA以Fluorescein-12-dUTP标记,探针显绿色荧光;正常胎盘组织以Tetramethylrhodamine-5-dUTP标记,探针显红色荧光),将标记的DNA探针同时与正常淋巴细胞分裂中期染色体进行杂交,杂交信号在荧光显微镜下经CCD(charge coupled device)摄像装置摄取,并通过荧光数字图像分析系统(quips CGH program)进行数据处理,计算两种荧光的比率并绘制分析图。结果：CNE2细胞存在广泛的染色体改变,主要表现在1q,3q,5p,6p,7p,8q,9q,11p,12q,19q的扩增和4q,12p,13p,14p,15p,18,20q,21p,22的缺失。从CNE2诱导的耐药细胞系CNE2／DDP恒定表现为8q,19q的扩增和8p的缺失,其它的染色体均未发现明显异常的扩增或缺失。将CNE2／DDP在不含药物的培养基中连续传代培养1个月后重复CGH,发现与连续药物处理的CNE2／DDP结果一致。CNE2／DDP细胞较CNE2细胞具有更为正常和稳定的染色体组成。结论：CNE2／DDP细胞是在耐药诱导过程中选择出来的单一的耐药细胞克隆。肿瘤细胞耐药的产生主要是一个克隆选择过程,即被诱导产生了耐药的细胞克隆在有药物存在的生存压力下被选择出来。     

Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma

Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5′-aza-2′ deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC- cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored.     

鼻咽癌染色体16q22-24遗传不稳定性的研究

目的：研究鼻咽癌染色体16q22-24的遗传稳定性。方法：用染色体16q22-24上的8对微卫星多态性标记分析50例鼻咽癌的杂合性缺失（loss of heterozygosity,LOH）与微卫星不稳定性（microsatellite instability,MSI)。结果：至少一个位点发生LOH的肿瘤占48％（24／50）,MSI的发生率为18％（9／50）。但这些变化均散在分布,未见高频共同缺失区和微卫星不稳定区;其变化在早期（Ⅰ/Ⅱ期）和晚期（Ⅲ/Ⅳ期）病人之间有显著性差异（P＜0．05）。结论：染色体16q22－24区的遗传不稳定性的变化可能与鼻咽癌的发病有关,该区是否存在鼻咽癌相关基因有待进一步探讨。     

Frequent chromosome 9p losses in histologically normal nasopharyngeal epithelia from southern Chinese

Nasopharyngeal carcinoma (NPC) is a common cancer among the Chinese population in the southern part of China. The incidence of this cancer drops markedly in northern China. A 6- to 24-fold difference exists between southern and northern Chinese. To investigate the early genetic events involved in the development of this cancer, we have examined loss of heterozygosity (LOH) on chromosome 9p, being one of the most frequent genetic alterations in NPC, in nasopharyngeal tissues including normal epithelia (NP), dysplastic lesions (DNP) and invasive carcinoma (NPC) from high-risk and low-risk regions. We found similar frequencies of 9p LOH in NPC from high-risk (77.8%) and low-risk (63.6%) regions (p = 0.43). In contrast, 45% of normal nasopharyngeal epithelia from the high-risk region showed 9p LOH, while none of the NP from the low-risk region showed such abnormalities (p = 0.002). Deletions of chromosome 9p were found in 66.7% dysplastic nasopharyngeal lesions. These findings suggest that LOH of chromosome 9p is an early event in the tumorigenesis of NPC. The increased risk of NPC in southern Chinese may be related to early loss of genetic materials as indicated by 9p LOH in the NP from high- and low-risk regions. We also reported previously that Epstein-Barr virus (EBV) latent infection was present in all high-grade DNP and NPC but not in any NP from fetuses or normal adults. Thus, early genetic alterations such as 9p LOH may take place prior to EBV latent infection and expand clonally thereafter.     

人鼻咽癌紫杉醇耐药细胞系与其亲代细胞系比较基因组杂交研究

目的：比较基因组杂交（comparative genomic hybridization, CGH）是一种在荧光原位杂交（fluorescence in situ hybridiza?tion,FISH）技术上发展起来的用于检测两个基因组间相对DNA拷贝数的改变（缺失或扩增）, 并将这些变化在染色体上进行定位的分子细胞遗传学方法。为了解鼻咽癌紫杉醇耐药细胞 （CNE1/Taxol, HNE2/Taxol, 5-8F/Taxol）与亲代细胞（CNE1, HNE2, 5-8F）在基因组DNA水平上可能存在的差异, 以及这种差异在肿瘤获得性耐药产生中的意义, 采用CGH技术对鼻咽癌紫杉醇耐药细胞与亲本细胞的基因组DNA进行检测和分析。方法：三株鼻咽癌紫杉醇耐药细胞采用大剂量冲击与剂量逐渐递加相结合的方法诱导而成。采用集落形成实验测定药物的敏感性,利用比较基因组杂交技术 （CGH） 对耐药细胞和其亲本细胞的基因组DNA进行检测和分析, 比较耐药细胞与亲本细胞在染色体扩增与缺失上的共同点和差异。结果：三株鼻咽癌紫杉醇耐药细胞耐药指数分别为8.43、 8.27和5.26。鼻咽癌亲本细胞存在广泛的染色体改变,主要表现在3q21-qter, 5p13-pter, 12和20q11-qter的共同扩增以及10q11-qter, 18和X染色体的共同缺失,从亲本细胞系诱导的三株鼻咽癌紫杉醇耐药细胞系表现为3q21-qter, 5p13-pter, 12,20q11-qter和8q21-qter的共同扩增, 无明显共同缺失区域。与亲本细胞共同扩增区域相比, 其中最有意义的是8q21-qter区域在三株耐药细胞中出现了新的共同扩增。结论： 3q21-qter, 5p13-pter, 12和20q11-qter的共同扩增以及10q11-qter,18和X染色体的共同缺失可能与鼻咽癌的发生有关, 而8q21-qter染色体扩增可能与鼻咽癌获得性紫杉醇耐药相关,对这些区域的进一步研究, 有可能为肿瘤发生及耐药机制研究提供新的线索。     

Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma

In previous studies, we successfully refined nasopharyngeal carcinoma (NPC) critical regions (CRs) mapping to chromosome 11q13 and 11q22-23. The chromosome 11 fragment containing the 1.8 Mb NPC CR at 11q13 (CR1), the CR at 11q22.3 mapped near D11S2000 (CR2), part of the CR at 11q23.1-11q23.2 overlapping with D11S1300 and D11S1391 (CR3), and the CR at cell adhesion molecule 1 (CADM1) locus (CR4), was chosen as the chromosome 11 donor cell line for the present study. Gamma irradiation was applied to cleave this truncated chromosome into smaller fragments and a new panel of donor cells containing further deleted fragments was produced. Subclones XMCH3.2 and XMCH3.4 were chosen for subsequent transfer to HONE1 cells; each contains a single copy of deleted chromosome 11 fragment with or without CR2 and the THY1 locus, previously shown to be involved in NPC. Both resultant chromosome 11 fragments in XMCH3.2 and XMCH3.4 caused tumor suppression. The association of alpha B-crystallin (CRYAB), a gene identified as being differentially expressed by gene profiling of NPC and an immortalized nasopharyngeal epithelial cell line, and which is located near CR3, was found to be associated with tumor suppression in all the tumor-suppressive hybrids. In addition, the expression level of this gene was down-regulated in the 7 NPC cell lines and in 5 out of 14 normal/tumor tissue pairs in the present study. Both promoter hypermethylation and allelic loss may be involved in the inactivation of this gene, suggesting its possible role in NPC development.     

Construction of evolutionary tree models for renal cell carcinoma from comparative genomic hybridization data

Renal cell carcinoma is characterized by an accumulation of complex chromosomal alterations during tumor progression. Chromosome 3p deletions are known to occur early in the carcinogenesis, but the nature of subsequent events, their interrelationships, and their sequence is poorly understood, as one usually only obtains a single "view" of the dynamic process of tumor development in a particular cancer patient. To address this limitation, we used comparative genomic hybridization analysis in combination with a distance-based and a branching-tree method to search for tree models of the oncogenesis process of 116 conventional (clear cell) renal carcinomas. This provides a means to analyze and model cancer development processes based on a more dynamic model, including the presence of multiple pathways, as compared with the fixed linear model first proposed by Vogelstein et al. (N. Engl. J. Med., 319: 525-532, 1988) for colorectal cancer. The most common DNA losses involved 3p (61%), 4q (50%), 6q (40%), 9p (35%), 13q (37%), and Xq (21%). The most common gains were seen at chromosome 17p and 17q (20%). The tree model derived from the distance-based method is consistent with the established theory that -3p is an important early event in conventional (clear cell) renal cancer and supports the prediction made from the branching tree that -4q is another important early event. Both tree models suggest that there may be two groups of clear cell renal cancers: one characterized by -6q, +17q, and + 17p, and another by -9p, -13q, and -18q. Putative prognostic parameters were -9p and -13q. The distance-based tree clarifies that -8p (present in 12% of tumors) is a late event, largely independent of other events. In summary, tree modeling of comparative genomic hybridization data provided new information on the interrelationships of genetic changes in renal cancer and their possible order, as well as a clustering of these events. Using tree analysis, one can derive a more in-depth understanding of the renal cancer development process than is possible by simply focusing on the frequencies of genetic events in a given cancer type.     

Genetic changes in colorectal carcinoma tumors with liver metastases analyzed by comparative genomic hybridization and DNA ploidy

BACKGROUND: Liver metastases are found in 10% of primary colorectal malignancies, and they affects the prognosis of patients with colorectal carcinoma. The authors investigated DNA copy number aberrations by using comparative genomic hybridization (CGH) and DNA ploidy alterations by using flow cytometry (FCM) in patients with primary colorectal carcinoma (primary tumors). To determine whether there are characteristic DNA copy number alterations that contribute to liver metastasis, cytogenetic aberrations were examined by CGH and FCM. METHODS: The authors analyzed 35 primary tumors, including 16 primary tumors with liver metastasis, by using CGH and FCM. RESULTS: Increases in DNA copy numbers were detected in 6q (5 of 16 tumors), 7q (6 of 16 tumors), 8q (7 of 16 tumors), 9p (5 of 16 tumors), 13q (8 of 16 tumors), 20p (9 of 16 tumors), and 20q (15 of 16 tumors) in primary tumors with liver metastases. Decreases in DNA copy numbers were found in 17p (5 of 16 tumors), 18p (6 of 19 tumors), 18q (8 of 16 tumors), and 22q (5 of 16 tumors). In contrast, primary tumors without liver metastasis showed gains in chromosome arms 8q (2 of 19 tumors), 13q (2 of 19 tumors), 20p (6 of 19 tumors), and 20q (5 of 19 tumors); however, they showed no gains in 6q or 7q and showed losses in chromosome arms 17p (2 of 19 tumors), 18p (4 of 19 tumors), 18q (6 of 19 tumors), and 22q (5 of 19 tumors). There was a significant difference in the frequency of DNA copy number gains and losses in 6q (P < 0.05), 7q (P < 0.01), 8q (P < 0.05), 13q (P < 0.05), and 20q (P < 0.01), respectively, between primary tumors with and without liver metastases. The differences in the DNA index were not significant between the two groups of primary tumors. CONCLUSIONS: In liver metastases of primary tumors from patients with colorectal carcinoma, a correlation between DNA copy number aberrations and gains of chromosome arms 6q, 7q, 8q, 13q, and 20q is suggested.     

p16基因缺失与鼻咽癌预后的相关性

[目的]探讨p16基因缺失在鼻咽癌中的临床意义。[方法]采用多重PCR分析法,对157例鼻咽癌标本p16基因突变情况进行检测。[结果]鼻咽癌组织中p16基因第2外显子的缺失率为35.0%（55/157）。p16基因第2外显子的缺失与鼻咽癌的临床分期、性别、年龄无显著性相关,但生存期〈3年者的p16基因第2外显子的缺失率高于生存期〉3年者（69.57%vs.29.10%,χ^2=14.12,P=0.000）。[结论]p16基因第2外显子可能与鼻咽癌的发生、发展和预后有关。     

用芯片技术分析鼻咽癌周围的基质细胞基因表达特点

背景与目的：鼻咽的基质细胞是如何参与鼻咽癌的癌变过程一直是研究的热点,本研究利用芯片技术分析鼻咽癌周围的基质细胞基因表达特点。探讨基质细胞在鼻咽癌发生和发展中的可能机制。方法：采用atlas human select tumor array滤膜,通过比较鼻咽癌组织和鼻咽癌细胞系的基因表达谱,获得鼻咽癌周围的基质细胞基因表达特点。结果：鼻咽癌周围的基质细胞至少可以特异地表达40个基因显示。结论：鼻咽癌周围的基质细胞具有基因的特异表达。