Analysis of genetic copy number changes in cervical disease progression.

Analysis of genetic copy number changes in cervical disease progression.
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DOI:
10.1186/1471-2407-10-432
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发表时间:
2010-08-16
期刊:
影响因子:
3.8
通讯作者:
Sokolova IA
Sokolova IA
中科院分区:
医学2区
文献类型:
--
作者:
Policht FA;Song M;Sitailo S;O'Hare A;Ashfaq R;Muller CY;Morrison LE;King W;Sokolova IA

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宫颈不典型增生和肿瘤的发生与大量的染色体异常有关。这项研究的目的是评估35个与宫颈疾病相关的基因组区域,并选择那些被发现具有最高异常频率的区域作为荧光原位杂交的探针。用荧光原位杂交法对30例石蜡包埋的宫颈活检标本的这35个区域的得失频率进行了评估。在此基础上,选择了6个候选荧光标记探针(8q24、Xp22、20q13、3p14、3q26、CEP15),对106例诊断为正常、CIN1、CIN2、CIN3和SCC的宫颈活检标本进行了额外的检测。根据信号平均值、不同组织学类型间信号平均值的变化百分比和阳性百分率对数据进行分析。研究发现,在高度宫颈疾病中,拷贝数增加频率最高、联合敏感性和特异性最高的染色体区域是8q24和3q26。然后对118例被诊断为正常、ASCUS、LSIL、HSIL和癌症的ThinPrep™样本进行细胞学应用评估,以确定作为一种较小侵入性筛查工具的实用性。以8q24或3q26的增益作为阳性标准,以4个阳性细胞为阈值,特异性(正常+LsIL+ASCUS)为81.0%,敏感性(HSIL+癌)为92.3%。由染色体探针8q24和3q26组成的FISH分析在宫颈细胞学标本中的应用证实了异型增生增加与复制增加之间的正相关,并显示出作为宫颈疾病进展的标志物的前景。
Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization. The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity. The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells. The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.
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发表时间: 1999-06-01
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