共查询到20条相似文献,搜索用时 250 毫秒
1.
p53基因点突变与胃粘膜细胞癌变的关系 总被引:11,自引:0,他引:11
目的研究p53基因在胃粘膜细胞癌变过程中的变异方式和类型。方法选取56例胃镜活检胃粘膜病变组织标本(胃癌23例,异型增生16例,肠上皮化生17例),应用单链构象多态性(SS-CP)和DNA序列分析等技术,对p53基因点突变的方式和类型进行检测和分析。结果p53基因在胃癌、异型增生和肠上皮化生组织中点突变频率较高,分别为60.1%、31.3%和11.8%,点突变分布在第5~8外显子,无突变热点。错义突变(73.9%)和移码突变占全部突变的86.9%。结论p53基因点突变是胃粘膜细胞癌变过程中多因素作用的结果,错义和移码突变可能是其失活的主要原因,p53基因点突变频率在肠型胃癌发展进程中呈渐进趋势,进一步明确了p53基因变异是胃粘膜细胞癌变过程中的一个重要因素。 相似文献
2.
p53基因突变及染色体倍性与大肠癌转移之间关系初探 总被引:2,自引:0,他引:2
目的研究大肠癌转移与p53基因突变及染色体倍性之间的关系。方法采用特异合成引物对p53基因的有关外显子进行PCR扩增,结合单链构象多态性(SSCP)和银染技术,检测15例大肠癌手术标本p53基因的突变;使用流式细胞仪(FACS)分析其染色体的倍性。结果8例有转移灶大肠癌病人中7例表现有p53基因的突变,而7例未转移大肠癌病人只显示3例有p53基因的突变。异倍体的9例病人中7例有p53基因突变,二倍体的6例病人中有3例有p53基因突变。结论大肠癌转移与p53基因突变细胞染色体异倍性三者相互存在着密切联系 相似文献
3.
p53基因突变与人非小细胞肺癌临床病理生理分析 总被引:1,自引:0,他引:1
目的 探讨p53基因点突变与人非小细胞肺癌临床生理特征的联系。方法 应用聚合酶反应-单链构象多态性分析方法(PCR-SSCP0检测原发性非小细胞肺癌癌组织的p53基因第5~8外显子点突变。结果 40例肺癌组织中19例(47.5%)有点突变发生,8例良性肿瘤组织均无p53基因点突变发生,点突变发生与病理分期和淋巴结转移有明显关系(P〈0.025),结论p基因估变在非小细胞肺癌的发生和进展中可能起重要作用。 相似文献
4.
目的 探讨p53基因点突变在非小细胞肺癌中的发生情况及临床病理联系。方法 运用聚合酶链反应(PCR)-单链构象多态性分析方法(SSCP)检测原发性非小细胞肺癌的p53 基因第5-8外显子点突变。结果 8例良性肿瘤均无点突变发生,40 例肺癌中19例(47.5% )有点突变发生,点突变发生与临床分期和淋巴结累及程度明显相关(P< 0.02)。结论 p53基因点突变在非小细胞肺癌的发生和进展中起着相当重要的作用。 相似文献
5.
目的:利用我们前期构建的溶瘤腺病毒SG600技术平台,研究其携带野生型p53基因对裸鼠胃癌移植瘤模型抗肿瘤活性。方法:克隆p53基因全长cDNA,插入到溶瘤腺病毒SG600基因组中,同时建立裸鼠胃癌移植瘤模型,体内观察SG600-p53对胃癌移植瘤模型的抗肿瘤疗效。结果:成功构建溶瘤腺病毒SG600-p53,裸鼠胃癌移植瘤的p53基因获增强表达。在胃癌移植瘤裸鼠模型中,经4周治疗,重组SG600-p53抑瘤率达 75.59%,优于Ad-p53(45.00%)和SG600(56.95%)。结论:SG600-p53作为一种有效的抗肿瘤新型制剂,对胃癌移植瘤有很好的特异性抗肿瘤活性,可能具有良好的临床应用前景。 相似文献
6.
肝细胞癌肿瘤抑制基因p53过度表达及点突变的研究 总被引:4,自引:0,他引:4
应用一种敏感的ARF免疫组经和PCR、银染PCR-SSCP方法检测了本地区38例肝细胞癌组织中肿瘤抑制基因p53的过度表达及点突变,结果发现16例有p53蛋白过度表达(41.2%),7例有p53基因249位密码子点突变,2例249位密码子外第7外显子点突变。9例p53基因有突变的肝癌中8例p53蛋白阳性,两者符合率为88.9%,p53基因蛋白过度表达和点突点与HCC分化和转移有关。本组HCC p5 相似文献
7.
肺癌患者癌组织和痰液细胞中p53和K-ras基因突变的研究 总被引:1,自引:0,他引:1
目的 检测肺癌组织和肺癌患者痰液脱落细胞中p53、K-ras基因突变情况,比较联合检测p53、K-ras和单一检测p53或K-ras基因在肺癌诊断中的价值。方法 应用PCR-SSCP-银染法检测了59例肺癌组织、癌旁肺组织、14全肺部良性病变肺组织及患者痰液脱落细胞中p53基因第5~8外显子、K-ras基因第1外显子突变。结果 肺癌组织中p53基因突变率为37.3%(22/59),痰液脱落细胞为3 相似文献
8.
目的:观察非小细胞肺癌(NSCLC)患者XRCC1基因399位点多态性以及吸烟对p53基因突变发生的影响。方法:运用不对称PCR技术扩增p53基因的第5~8外显子,用聚合酶链反应 单链构象多态性分析法(PCR-SSCP)检测p53基因突变,并对有差异的结果测序验证;运用PCR技术扩增XRCC1基因的第10外显子,从正反两个方向对扩增片段进行DNA测序分析其多态性;同时了解吸烟与它们的关系。结果:38例可手术的NSCLC患者中发现16例有p53基因的突变,发生突变的16例中6例至少携带1个XRCC1-399Gln等位基因,10例为野生基因型XRCC1-399Arg/Arg,用二项分类Logistic回归模型分析XRCC1-399Gln多态性与p53基因突变两者的关系,优势比(OR)为1.536(95%CI:0.376~6.280);该模型中吸烟与p53基因突变的OR为1.524(95%CI:0.250~9.295)。结论:NSCLC患者中,XRCC1基因399位点多态性和吸烟情况对p53基因突变发生无明显影响。 相似文献
9.
外源p53对人肺癌细胞生长的抑制 总被引:2,自引:0,他引:2
目的 观察外源性野外型p53对有p53基因突变的人肺癌细胞系生长的影响。方法 用PCR-SSCP及DNA测序,选择p53突变的人肺巨细胞癌系801-D。构建野生型p53表达质粒PZiP-p53。用基因枪介导外源基因。经G418筛选得到转染细胞系801-D-p53。用PCR检测外源基因,观察转染细胞恶性生长的变化。结果 转染细胞系801-D-p53体外长期传代有外源性p53基因存在,转染细胞生长明显 相似文献
10.
胃癌组织p53基因缺失和异常表达 总被引:5,自引:0,他引:5
检测20例行胃癌根治手术患者的癌组织和对应的正常粘膜组织中p53基因DNA结构和蛋白表达。Southern印迹显示30%(6/20)的胃癌组织中存在p53基因部分缺失。应用抗p53单克隆抗体-PAb1801和ABC免疫组织化学技术检测冰冻切片组织中p53蛋白的表达,结果表明,55%(11/20)胃癌组织中存在突变p53蛋白高表达,阳性染色部位位于细胞核和/或细胞浆中,所有正常组织标本中均未见阳性染色,低分化腺癌p53阳性表达率显著高于分化好的胃癌(P=0.0116),p53蛋白高表达和等位基因缺失密切相关(r=0.59)。结果提示,在人类胃癌形成和肿瘤演进过程中,p53基因失活是一个重要的事件,p53基因结构和产物的变化可以作为新的肿瘤相关标志,这对判断胃癌生物学行为,识别具有高度恶化倾向的肿瘤,估价胃癌病员的预后和指导临床治疗有一定的作用。 相似文献
11.
Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood. In this study, we applied laser capture microdissection (LCM) microscope to histologically review and sample cells from paraffin-embedded breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS) and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected, using single stranded conformational polymorphism (SSCP) and sequencing, in cell samples of three cases with DCIS and five cases with ADH. p53 mutations are therefore present in DCIS and ADH of the breast, considered as pre-malignant precursors to breast cancer, and some of them may represent early events in breast cancer development. 相似文献
12.
应用PCR-SSCP银染技术分析胃癌p53基因的点突变 总被引:1,自引:1,他引:1
目的 分析胃癌中p53基因第5-8外显子点突变的发生及其意义。方法 应用聚合酶链反应-单链构象多态性分析(PCR-SSCP)和银染技术,对40例胃良性疾病和30例胃癌标本中p53基因第5-8外显子的点突变情况进行检测。结果 40例胃良性疾病均无点突变发生,30例胃癌中有12例发生p53基因的点突变,突变率为40.00%(12/30)。结论 p53基因突变与胃癌的发生密切相关;PCR-SSCP银染技术不仅灵敏安全,而且简便、快速、重复性好,可用于临床的基因诊断。 相似文献
13.
Predictive value of Ki-67, p53 protein, and DNA content in the diagnosis of gastric carcinoma. 总被引:11,自引:0,他引:11
BACKGROUND: The ability to make a precise preoperative diagnosis is a valuable and effective method in improving the prognosis of patients with gastric carcinoma. The authors examined retrospectively whether preoperative histopathologic analysis with p53 protein, Ki-67 labeling index, and DNA ploidy along with preoperative radiographic and endoscopic findings led to a precise preoperative diagnosis of patients with gastric carcinoma. METHODS: Histopathologic analysis of p53 protein, Ki-67 labeling index, and DNA content was performed on formalin fixed, paraffin embedded tissue. Tissue sections from endoscopic and surgically resected specimens were stained immunohistochemically for p53 protein and Ki-67 labeling index, and the cell nuclear DNA content of the surgically resected primary lesion was measured using a microspectrophotometer. These analyses were performed on 16 patients with early gastric carcinoma (EGC) who were diagnosed with advanced gastric carcinoma (AGC) based on the preoperative imaging findings and on 15 patients with AGC who were diagnosed preoperatively with EGC. RESULTS: Overexpression of p53 in the AGC group was significantly more frequent compared with that in the EGC group (P = 0.0386). With regard to the correlation between lymph node metastases and p53 overexpression, there was no apparent relation in either the AGC group (P = 0.648) or the EGC group (P = 0.726). The AGC group had significantly higher Ki-67 labeling indices compared with the EGC group (P = 0.0195). There was complete concordance between endoscopic and surgically resected specimens with regard to the p53 and Ki-67 labeling index findings. DNA ploidy in the primary tumor did not differ between the AGC and EGC groups. The survival rates for the EGC group were significantly superior to those for the AGC group (P = 0.0312). CONCLUSIONS: The findings of the current study suggest that in routine clinical practice, the combination of preoperative imaging findings in addition to Ki-67 labeling indexes, and p53 protein analyses may be useful for the accurate diagnosis of EGC; however, DNA ploidy did not appear to reflect the growth potential of gastric carcinoma. 相似文献
14.
Fricke E Keller G Becker I Rosivatz E Schott C Plaschke S Rudelius M Hermannstädter C Busch R Höfler H Becker KF Luber B 《International journal of cancer. Journal international du cancer》2003,104(1):60-65
E-cadherin mutations are found in 50% of diffuse-type gastric carcinoma, but not in intestinal gastric carcinoma. Because cell-cell adhesion mediated by E-cadherin plays an important role in epithelial cell survival, E-cadherin mutations could alter the apoptotic behavior of tumor cells. p53 and Bcl-2 family members are also important regulators of cellular apoptosis. This is the first study that investigates the relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression, and Ki-67 expression in diffuse-type gastric carcinoma (24 cases, E-cadherin mutation status: wild-type in 8 patients and mutant in 16 patients). The mutation status of exons 5-8 of p53 was analyzed by denaturing high pressure liquid chromatography (DHPLC) in formalin-fixed, paraffin-embedded tumor sections, followed by direct sequencing of cases with aberrant chromatographic patterns. p53 mutations were found in 1 of 8 tumors without E-cadherin mutation (12.5%) and in 1 of 16 tumors with E-cadherin mutation (6.3%), a difference that was not statistically significant (p = 1.00). p53 accumulation was found in 8 of 24 tumors (33.3%) by immunohistochemical staining. p53 accumulation was significantly more frequent in tumors without E-cadherin mutations (5 of 8 tumors, 62.5%) than in gastric carcinoma tissues with E-cadherin mutations (3 of 16 tumors, 18.8%, p = 0.03). Bcl-2 staining was not observed in gastric carcinoma cells without E-cadherin mutations, but was detectable in 5 of 16 tumors with E-cadherin mutations (31.3%), a difference that was not statistically significant (p = 0.13). No relationship was observed between Ki-67 staining and the E-cadherin mutation status (p = 1.00). These data suggest that the presence of E-cadherin mutations can significantly alter the accumulation of the apoptosis-regulating p53 protein, whereas no correlation with the p53 mutation status or with Ki-67 staining was observed. 相似文献
15.
Kim SK Cho BK Paek SH Hong SJ Kim HS Hong SY Choe G Chi JG Nam DH Wang KC 《International journal of oncology》2001,18(1):111-116
Using a microdissection technique, the contribution of the p53 mutation to tumorigenesis and prognosis in each histological subtype of the intracranial germ cell tumors (GCTs) was evaluated. Nineteen patients had primary intracranial GCTs, including 4 germinomas (GEs), 4 teratomas (TEs), 1 mixed tumor of GE and TE, and 10 mixed GCTs containing non-germinomatous malignant germ cell tumors (NG-MGCTs). After microdissection of specific subtypes, genomic DNA was screened for mutations in exons 5-8 of the p53 gene, using the dideoxyfingerprinting (ddF) followed by direct DNA sequencing. The direct sequencing revealed a total of six mutations in PCR products derived from the five cases (26%) which showed mobility shifts in ddF. Among the six mutations detected, four were missense mutations and two were silent. Missense mutations of the p53 gene tended to occur more frequently in the NG-MGCT component than in the GE or TE components (3/15 vs. 1/12 vs. 0/13). The incidence of missense mutations was not different between the survivors (3/13) and the deceased (1/6). This study suggests the possible role of the p53 gene in the tumori-genesis of NG-MGCT. However, p53 gene mutation did not correlate with the prognosis of NG-MGCT. 相似文献
16.
Oki E Tokunaga E Nakamura T Ueda N Futatsugi M Mashino K Yamamoto M Watanabe M Ikebe M Kakeji Y Baba H Maehara Y 《Cancer letters》2005,227(1):33-38
Both PTEN (encoding phosphate and tensin homologue) and p53 are known as cancer suppressor genes, and they are assumed that their gene mutations and loss of heterozygosity (LOH) occur frequently in various types of carcinoma. In the present study, we investigated both the p53 mutation and LOH of PTEN in 113 gastric cancer patients. We observed the LOH of PTEN in 11.1% of the patients with normal p53s and 46.2% of the patients with p53 gene mutations. The result that LOH of PTEN was frequently observed in the cases with p53 gene mutations and other data in this study suggested that both PTEN and p53 have complimentary roles in gastric carcinoma development. 相似文献
17.
Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and <Emphasis Type="Italic">p53</Emphasis> gene alteration 总被引:4,自引:0,他引:4
Ken Nishikura Hidenobu Watanabe Mitsuya Iwafuchi Takato Fujiwara Kazuko Kojima Yoichi Ajioka 《Gastric cancer》2003,6(4):203-209
Background Endocrine cell carcinoma of the stomach is characterized by endocrine differentiation and aggressive biological behavior, and is frequently accompanied by an adenocarcinoma component. Because the carcinogenic pathway and genetic alterations remain unclear, we investigated the histogenesis of this tumor by histopathological and p53 gene analysis.Methods The materials were 68 gastric endocrine cell carcinomas and 30 carcinoid tumors, which were resected from 93 Japanese patients for histopathological and immunohistochemical investigation. We also analyzed the concordance of p53 mutational status between the associated adenocarcinoma and endocrine cell carcinoma components, using microdissection and direct sequencing techniques.Results An adenocarcinoma component was associated with 70.6% (48/68) of endocrine cell carcinomas, of which 42 (87.5%) were of well- to moderately differentiated type, while 36 of these 42 (85.7%) demonstrated histological continuity with the endocrine cell carcinoma components. Overexpression of p53 protein was observed in 58.8% (20/34) of cases. Common p53 mutational status between the two components was revealed in 73.3% (11/15) of cases analyzed. In contrast, carcinoid tumors did not exhibit p53 protein overexpression (0/15) or gene mutation (0/5).Conclusions These data suggest that gastric endocrine cell carcinomas predominantly arise from endocrine precursor cell clones occurring in preceding adenocarcinoma components (particularly the differentiated type), transforming into endocrine cell carcinoma during rapid clonal expansion under the influence of p53 gene alteration. 相似文献
18.
Matteo Fassan Michele Simbolo Emilio Bria Andrea Mafficini Sara Pilotto Paola Capelli Maria Bencivenga Sara Pecori Claudio Luchini Diogo Neves Giona Turri Caterina Vicentini Licia Montagna Anna Tomezzoli Giampaolo Tortora Marco Chilosi Giovanni De Manzoni Aldo Scarpa 《Gastric cancer》2014,17(3):442-449
Background
There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC).Methods
HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes.Results
Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations. TP53 mutations were observed in 9 cases; APC mutations were identified in 3 cases; and ATM and STK11 were mutated in 2 cases. Seven HG-IEN lesions shared an identical mutational profile with the EGC from the same patient; 13 mutations observed in APC, ATM, FGFR3, PIK3CA, RB1, STK11, and TP53 genes were shared by both HG-IEN and ECG lesions. CDKN2A, IDH2, MET, and RET mutations were observed only in EGC. TP53 deregulation was further investigated in an independent series of 75 biopsies corresponding to all the phenotypic lesions occurring in the EGC carcinogenetic cascade. p53 nuclear immunoreaction progressively increased along with the dedifferentiation of the lesions (P < 0.001). Overall, 18 of 20 p53-positive lesions showed a TP53 mutated gene.Discussion
Our results support the molecular similarity between HG-IEN and EGC and suggest a relevant role for TP53 in the progression to the invasive phenotype and the use of immunohistochemistry as a surrogate to detect TP53 gene mutations. 相似文献19.
Ito S Ohga T Saeki H Nakamura T Watanabe M Tanaka S Kakeji Y Maehara Y 《International journal of cancer. Journal international du cancer》2005,113(1):22-28
Inactivation of the p53 tumor suppressor gene is one of the most frequent genetic alterations observed in human esophageal carcinomas. In patients with esophageal carcinoma, one of the significant pathological features of the tumor is the presence of multiple lesions within the esophagus. However, the molecular mechanisms involved in the occurrence of multiple lesions have remained elusive. To characterize p53 alterations in multiple esophageal carcinomas and to study their roles in carcinogenesis, we performed p53 immunohistochemical and p53 mutation analyses using laser capture microdissection on surgically resected human esophageal carcinomas from 11 patients: 9 patients with multiple esophageal carcinomas, 1 with an intramural metastasis lesion within the esophagus and 1 with an intraepithelial carcinoma lesion contiguous to the main lesion. In each of the patients with multiple esophageal carcinomas, we examined samples from 1 main lesion and 1 representative concomitant lesion. Molecular analyses of samples from fresh-frozen normal tissues and tumor tissues of the main lesion (whole tumor) were also performed by the same method. p53 protein accumulation was observed in 16 (72.7%) of 22 lesions from the 11 cases. No p53 mutation was found in normal esophageal tissues. In the 9 cases of multiple esophageal carcinomas, point mutations were detected in the whole tumor in 1 (11.1%) case, in the microdissected tumor samples of main lesions in 3 (33.3%) cases and in the microdissected tumor samples of concomitant lesions in 3 (33.3%) cases. For the microdissected tumor samples, there was a 54.5% (12/22) concordance rate between the results of immunostaining and molecular analysis. In the 8 cases of whole tumors in which a p53 mutation was not observed, 2 cases revealed p53 mutation in the microdissected tumor samples of the main lesion. All 6 cases of multiple esophageal carcinomas that showed a p53 mutation in the microdissected tumor sample had a discordant p53 mutational status between the main and concomitant lesions. In contrast, both the intramural metastasis lesion and the intraepithelial carcinoma contiguous to the main lesion showed p53 mutational patterns identical to those of the main lesions. In conclusion, the analysis of microdissected DNA by laser capture microdissection is useful for characterizing the heterogeneity of the p53 gene mutation in multiple carcinoma lesions that cannot be accurately analyzed in whole esophageal tumor DNA. The finding of different p53 gene mutations among multiple esophageal carcinoma lesions suggest further evidence of multicentric or field carcinogenesis of the human esophagus. 相似文献
20.
J H Kim T Takahashi I Chiba J G Park M J Birrer J K Roh H De Lee J P Kim J D Minna A F Gazdar 《Journal of the National Cancer Institute》1991,83(13):938-943
We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma. 相似文献