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8号染色体微卫星位点的杂合性缺失表明在人前列腺癌中,D8S87和D8S133位点之间存在一个候选肿瘤抑制基因。

Loss of heterozygosity of chromosome 8 microsatellite loci implicates a candidate tumor suppressor gene between the loci D8S87 and D8S133 in human prostate cancer.

作者信息

Trapman J, Sleddens H F, van der Weiden M M, Dinjens W N, Konig J J, Schroder F H, Faber P W, Bosman F T

机构信息

Department of Pathology, Erasmus University, Rotterdam, The Netherlands.

出版信息

Cancer Res. 1994 Dec 1;54(23):6061-4.

PMID:7954446
Abstract

To search for specific chromosome 8 aberrations in human prostate cancer, DNA was isolated from 44 human prostate tumor samples. Twenty six tumor samples were obtained from locally progressive tumors by transurethral resection, 12 were from radical prostatectomy specimens, and 6 were from lymph node metastases. Tumor DNAs were screened for allelic losses using 16 highly polymorphic microsatellite loci (14 covering the p arm, 2 on the q arm). In general, the detected deletions were large. In 59% of the tumor DNAs, allelic loss of 3 or more 8p loci was observed. Loss of 8p loci occurred in between 36 and 69% of the informative cases; for the two 8q markers, the percentages of loss were 11 and 25%, respectively, indicating preferential loss of (part of) 8p. In one tumor, two separate 8p deletions were found. The percentage of loss of heterozygosity was considerably higher in transurethral resection (65%) and lymph node metastases (83%) than in radical prostatectomy specimens (33%), suggesting that 8p deletion is a relatively late step in tumor progression. The maximal overlapping deleted region in all tumor DNAs is between the distal locus D8S133 and the proximal locus D8S87, indicating the localization of a candidate tumor suppressor gene within this region.

摘要

为了在人类前列腺癌中寻找特定的8号染色体畸变,从44例人类前列腺肿瘤样本中提取了DNA。26例肿瘤样本通过经尿道切除术从局部进展性肿瘤中获取,12例来自前列腺癌根治术标本,6例来自淋巴结转移灶。使用16个高度多态性微卫星位点(14个覆盖p臂,2个在q臂)筛选肿瘤DNA的等位基因缺失情况。一般来说,检测到的缺失片段较大。在59%的肿瘤DNA中,观察到3个或更多8p位点的等位基因缺失。8p位点缺失发生在36%至69%的信息性病例中;对于两个8q标记,缺失百分比分别为11%和25%,表明8p(部分)优先缺失。在一个肿瘤中,发现了两个独立的8p缺失。经尿道切除术(65%)和淋巴结转移灶(83%)中杂合性缺失的百分比明显高于前列腺癌根治术标本(33%),这表明8p缺失是肿瘤进展中相对较晚的步骤。所有肿瘤DNA中最大的重叠缺失区域在远端位点D8S133和近端位点D8S87之间,表明候选肿瘤抑制基因定位于该区域内。

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