肾母细胞瘤WT1基因缺失

目的：对30例散发性肾母细胞瘤WT1基因缺失进行检测,并分析其与组织类型的关系。方法：采用Southern印迹分子杂交技术,结果2例WT1基因内缺失为持质优势型肾母细胞瘤,结论：肾母细胞瘤的病因十分复杂,WT1基因缺失可能 与间质优势型肾母细胞瘤的发生有关。     

24例肾母细胞瘤WT1基因突变筛查

目的筛查WT1基因在肾母细胞瘤中的改变情况。方法我们采用PCR－SSCP技术及多重PCR方法对24例肾母细胞瘤标本WT1基因第4，6－10外显子进行筛查。结果发现2例标本存在SSCP电泳迁移率的异常。应用双重PCR方法证实一例为WT1基因第8外显子的纯合性缺失。结论提示WT1基因多种形式的突变均可导致肾母细胞瘤的发生，但可能并不是导致散发型肾母细胞癌发生的主要因素。     

24例肾母细胞瘤WT1基因突变筛查

目的筛查ＷＴ１基因在肾母细胞瘤中的改变情况。方法我们采用ＰＣＲ－ＳＳＣＰ技术及多重ＰＣＲ方法对２４例肾母细胞瘤标本ＷＴ１基因第４，６－１０外显子进行筛查，结果发现２例标本存在ＳＳＣＰ电泳迁移率的异常。应用双重ＰＣＲ方法证实一例为ＷＴ１基因第８外业子的纯合性缺失。结论提示ＷＴ１基因多种形式的突变均可导致肾母细胞瘤的发生，但可能并不是导致散发型肾母细胞瘤的主要因素。     

RFLP法检测IGF2和H19基因胚胎印迹缺失

目的探讨肾母细胞瘤的发生、发展与IGF2和H19基因胚胎印迹缺失（LOI）的关系。方法PCR－RFLP法检测6例肾母细胞瘤中IGF2和H19的等位基因表达。结果6例中3例存在IGF2基因的LOI，而H19基因的LOI仅为1例，并且，这两种基因的LOI均可在I期肿瘤内被检测到。结论提示肾母细胞瘤的发生与IGF2基因的LOI有密切关系；这种胚胎印迹紊乱可发生在肿瘤的早期。     

WT1在乳腺癌中的研究进展

Wilms瘤基因1(Wilms' tumor gene 1,WT1)作为抑癌基因第一次在肾母细胞瘤(又称 Wilms瘤)中被描述,但后续的研究表明WT1基因在多种肿瘤中高表达,包括乳腺癌、肺癌、直肠癌,提示WT1可能具有癌基因的作用。多项研究显示,WT1与乳腺癌的发生、发展及预后密切相关。因此WT1有助于揭示乳腺癌发生发展的机制,并成为乳腺癌潜在的生物治疗靶位。本文就近年来WT1在乳腺癌中的研究进展予以综述。     

肾母细胞瘤发病机制的研究进展

肾母细胞瘤是最常见的儿童原发性泌尿系统恶性肿瘤,具有早期诊断难、预后欠佳、易复发等特点.研究表明具有肾母细胞瘤倾向的综合征、肾母细胞瘤发病机制相关的基因通路(WT1、WTX、TP53、MYCN及基因拷贝数变异等)、表观遗传机制(印记基因、甲基化)、MicroRNAs、DNA错配修复系统等多种因素均参与肾母细胞瘤的发生发展,但一些结论仍然需要大量基础和临床研究来支持.肾母细胞瘤发病机制纷繁复杂,应充分利用现有研究进展,开展遗传咨询及个体化治疗.全文就近年来国内外对于肾母细胞瘤发病机制研究的最新进展作一系统综述.     

肾母细胞瘤中IGF-2外显子9甲基化状态与IGF-2表达关系的初步研究

目的：探讨胰岛素样生长因子 （IGF-2） 外显子9CpG岛甲基化状态与IGF-2基因表达的关系, 以进一步探究肾母细胞瘤发生机制。方法： 应用甲基化敏感性限制性内切酶PCR和等位基因特异性IGF-2基因表达分析, 检测42例肾母细胞瘤及相应正常组织的IGF-2外显子9甲基化状态及IGF-2基因表达。结果： 肾母细胞瘤IGF-2外显子9甲基化率为16.6 %, 瘤旁组织为95.2 %, 两者差异有统计学意义 （P<0.01）, 其中以胚基细胞为主型肾母细胞瘤IGF-2外显子9去甲基化率高于上皮细胞优势型和间质细胞优势型的肾母细胞瘤 （P<0.01）, 在低分化间变型肾母细胞瘤中IGF-2外显子9去甲基化率显著高于高分化无间变型肾母细胞瘤 （P<0.01）。外显子9去甲基化组织中IGF-2双等位基因表达率显著高于甲基化的组织 （P<0.05）。结论： 肾母细胞瘤IGF-2外显子9去甲基化可能是引起IGF双等位基因表达, 进一步导致肿瘤的发生发展的确切机制, 从肾母细胞瘤的发生发展分子机制方面为肾母细胞瘤的早期诊断和治疗提供新的理论依据。     

RFLP法检测IGF2和H19基因胚胎印迹缺失

「目的」探讨肾母细胞瘤的发生、发展与ＩＧＦ２和Ｈ１９基因胚胎印迹缺失的关系。ＰＣＲ－ＲＦＬＰ法检测６例肾母细胞瘤中ＩＧＦ２和Ｈ１９的等位基因表达。「结果」６例中３例存在在ＩＧＦ２基因的ＬＯＩ，而Ｈ１９基因ＬＯＩ仅为１例，并且，这两种基因的ＬＯＩ可在Ⅰ期肿瘤内被检测到。「结论」提示肾母细胞瘤的发生与ＩＧＦ２基因的ＬＯＩ有密切关系；这种胚胎印迹紊乱可发生在肿瘤的早期。     

恶性心包积液细胞蜡块联合基因检测在明确肿瘤来源及肺腺癌个体化治疗中的应用

目的 探讨恶性心包积液细胞蜡块联合基因检测在明确肿瘤来源及肺腺癌患者个体化治疗中的应用价值.方法 选择50例恶性心包积液标本作为研究对象,制备细胞蜡块,进行苏木素-伊红(HE)染色,同时选择钙网膜蛋白(CR)、间皮细胞(MC)、肾母细胞瘤基因1(WT1)、癌胚抗原M2A单克隆抗体(D2-40)、尾型同源盒转录因子2(C...     

肾母细胞瘤中p53的基因突变

目的：调查肾母细胞瘤中ｐ５３基因突变，探讨ｐ５３基因突变与肾母细胞瘤发生的关系。方法：采用ＰＣＲＳＳＣＰ分析结合ＤＮＡ直接测序对肾母细胞瘤病人手术标本进行ｐ５３基因第２～１１外显子的突变筛查。结果：２５例肿瘤标本中未检出缺失，７例显示有ＳＳＣＰ电泳迁移率的改变，其中３例经序列分析证实为错义突变，１例合并一同义突变。结论：ｐ５３基因突变涉及肾母细胞瘤的发生     

Aniridia--Wilms' tumour association--a case with 11p 13-14.1 deletion and ventricular septal defect.

A two year old female child with bilateral wilms tumor (WT) along with multiple congenital anomalies like bilateral aniridia with congenital cataracts and nystagmus, microcephaly, mental retardation and ventricular septal defect has been described. The karyotype analysis revealed 46 xx, del 11p 13-14.1. Association of ventricular septal defect with the classical features of 'Aniridia-Wilms' tumor association' is an unusual feature in this case.     

RNA expression of the WT1 gene in Wilms' tumors in relation to histology.

BACKGROUND: On the basis of accumulating data, the recently isolated WT1 gene is a Wilms' tumor gene and a putative tumor suppressor gene. These findings include expression in developing fetal kidney, intragenic deletions in tumors, and germline mutations in predisposed individuals. Wilms' tumors, which exhibit a broad range of differentiation, are composed of three cell types: blastema, epithelium, and stroma. PURPOSE: The purpose of this study was to investigate the relationship between WT1 gene expression and histologic composition in Wilms' tumors in an effort to elucidate how the WT1 gene functions in proliferation of these histologic components. METHODS: We used Northern blot hybridization to study WT1 gene expression by messenger RNA (mRNA) accumulation in 20 tumors of varying histology and in adjacent uninvolved kidney tissue. In two patients, tumors were also compared before and after therapy. RESULTS: Tumors that were predominantly blastemal expressed high amounts of WT1 mRNA, whereas predominantly stromal tumors expressed either low or undetectable amounts. Blastemal tumors that were predominantly poorly differentiated expressed WT1 mRNA at higher levels than those that were more well differentiated. Although we expected that a putative tumor suppressor gene like WT1 would generally be expressed at lower levels in tumor than in normal kidney, this was true only in predominantly stromal cells. One of the two patients studied before and after therapy had a dramatic response to therapy accompanied by a decline in WT1 gene expression and disappearance of blastemal and epithelial elements. CONCLUSIONS: A correlation was observed between WT1 gene expression and histology of the tumors. Level of expression was inversely related to the degree of differentiation in blastemal tumors and in the patient with a dramatic response to therapy. These results, in conjunction with the observation that WT1 mRNA is abundant in normal fetal kidney, suggest that WT1 gene expression is related to kidney development, especially in differentiation of blastemal components. IMPLICATIONS: Further studies to search for alterations of the WT1 gene in tumors and to identify regulatory factors in gene expression will increase understanding of the role of this gene in normal development and tumorigenesis.     

Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma

The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 antisense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product.     

Low Wilms' tumor gene expression in tumor tissues predicts poor prognosis in patients with non-small-cell lung cancer

We elucidated the relationship between prognosis of non-small-cell lung cancer (NSCLC) and Wilms' tumor gene (WT1) mRNA expression in tumor tissue. The WT1 mRNA expression levels of the fatal cases were lower as compared with those of the survival cases. Overall survival (OS) and disease-free survival (DFS) of the high WT1 expression group were longer than of the low expression group. As for squamous cell lung cancer (SQLC), low WT1 expression was significantly associated with lymph node metastasis. Cox analysis revealed that the gene level was a significant prognostic factor in OS and DFS. Low WT1 expression predicted poor prognosis in patients with NSCLC.     

WT1在上皮性卵巢癌中的表达及意义

目的探讨肾母细胞瘤基因(Wilms tumor gene,WT1)蛋白在上皮性卵巢癌中的表达及临床意义。方法采用免疫组织化学SP法检测50例卵巢上皮性癌、10例卵巢良性肿瘤和10例正常卵巢石蜡标本中WT1表达情况。应用SPSS13.0软件结合临床病理资料进行综合分析。结果正常及良恶性上皮性卵巢组织中WT1皆有表达,WT1在卵巢癌组织中的表达明显高于正常及良性卵巢组织(P<0.01),正常和良性卵巢组织中两者无显著性差异(P>0.05)。WT1在浆液性卵巢癌中表达率为93%(28/30),随着病理分级及临床分期的增高,WT1表达率逐渐增高。WT1阴性表达者生存时间明显比WT1阳性者长。WT1表达与病理分级、临床分期、组织学类型及预后明显相关(P<0.05),而与年龄、淋巴结转移无关(P>0.05)。结论WT1在卵巢癌组织中的表达明显高于正常及良性卵巢组织,在卵巢癌的浸润和转移中发挥了重要作用,可作为判断卵巢癌恶性程度及评估不良预后的重要指标。