Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum.
Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum.
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腹膜乳头状浆液性癌中 WT1 基因的遗传改变。
DOI：
10.1006/gyno.1999.5711
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Mok,SC
中科院分区：
文献类型：
--
作者：
Schorge,JO;Miller,YB;Qi,LJ;Muto,MG;Welch,WR;Berkowitz,RS;Mok,SC
目的在正常卵巢生发上皮和人卵巢间皮中一致检测到Wilms' tumor （WT1）基因产物。卵巢癌经常表现出WT1功能的改变。腹膜乳头状浆液性癌（PSCP）被认为是从骨盆和腹部的腹膜衬里（间皮层）重新发展而来的。本研究的目的是确定WT1基因的遗传改变是否与PSCP的发生有关。方法选取III期、IV期PSCP患者（38例）和浆液上皮性卵巢癌患者（38例）的正常组织和肿瘤组织标本。采用抗wt1 （C-19）抗体进行免疫组化。杂合性缺失（LOH）发生在WT1位点。获得临床数据并与分子发现相关联。结果35例PSCP标本中18例（51%）和34例卵巢癌标本中18例（53%）检测到WT1正常表达缺失。22例PSCP标本中有6例（27%）和24例卵巢癌标本中有3例（13%）在WT1位点存在LOH （P = 0.27）。WT1基因在86%的LOH肿瘤中保持正常表达。WT1基因的遗传改变不能预测生存率，也与其他临床或分子因素无关。结论WT1基因的遗传改变与PSCP的发生有关。WT1基因正常表达的缺失是PSCP和晚期卵巢癌的常见事件，可能是由于其他调节因子的下调，而不是由于失活基因突变和随后的等位基因丢失。
ObjectiveThe Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP.MethodsNormal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings.ResultsLoss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors.ConclusionsGenetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors—not from inactivating gene mutation and subsequent allelic loss.
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影响因子：
6
作者：
Chan, WY;Cheung, KK;Mok, SC
通讯作者：
Mok, SC
人类肾母细胞瘤基因 (WT1) 的转录调控。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fraizer,GC;Wu,YJ;Hewitt,SM;Maity,T;Ton,CC;Huff,V;Saunders,GF
通讯作者：
Saunders,GF
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DOI：
--
发表时间：
2000
期刊：
Cancer research.
影响因子：
--
作者：
Schorge,JO;Muto,MG;Lee,SJ;Huang,LW;Welch,WR;Bell,DA;Keung,EZ;Berkowitz,RS;Mok,SC
通讯作者：
Mok,SC
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DOI：
--
发表时间：
1982
期刊：
The Lancet
影响因子：
--
作者：
J. Tobacman;M. Tucker;R. Kase;M. Greene;Jose Costa;J. Fraumeni
通讯作者：
J. Fraumeni
侵袭性人类卵巢癌中染色体 11p13-11p15.5 序列的缺失是亚克隆进展因素。
影响因子：
11.2
作者：
B. Vandamme;Willy Lissens;K. Amfo;P. D. Sutter;Claire Bourgain;E. Vamos;J. D. Greve
通讯作者：
J. D. Greve