Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia
Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia
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DOI：
10.1016/s0002-9440(10)63498-0
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发表时间：
2003-10-01
影响因子：
6
通讯作者：
Ried, T
中科院分区：
文献类型：
--
作者：
Heselmeyer-Haddad, K;Janz, V;Ried, T
浸润性宫颈癌经常显示3号染色体长臂的额外拷贝。因此，在诊断样品中检测到这种遗传畸变可以补充形态学解释。我们已经开发了一种三色DNA探针组，用于通过荧光原位杂交直接在薄层宫颈细胞学切片中观察染色体拷贝数的变化。探针组由BAC重叠群组成，该BAC重叠群含有染色体带3q 26上的人端粒酶基因（TERC）的RNA组分的序列，以及作为对照的对染色体3和7的着丝粒特异的重复序列。在一项盲法研究中，我们分析了57个薄层切片，这些切片经过严格筛选并分为正常（n = 13）、非典型鳞状细胞（ASC，n = 5）、低度鳞状上皮内病变（LSIL，n = 14）和高度鳞状上皮内病变（HSM）2级（CIN 2，n = 8）和3级（CIN 3，n = 17）。四倍体细胞（P-Trend < 0.0005）和具有多个3q信号的细胞的百分比随着细胞学解释的严重性而增加（P-Trend < 0.0005）。虽然只有少数正常样本（ASC和LSIL病变）显示3q拷贝数增加，但63%的HSIL（CIN 2）病变和76%的HSIL（CIN 3）病变显示3q拷贝数增加。我们的结论是，可视化的染色体3q拷贝数在常规制备的细胞学材料中使用BAC克隆特异性TERC作为一个独立的筛选试验HSIL，并可能有助于确定个别病变的进展潜力。
Invasive cervical carcinomas frequently reveal additional copies of the long arm of chromosome 3. The detection of this genetic aberration in diagnostic samples could therefore complement the morphological interpretation. We have developed a triple-color DNA probe set for the visualization of chromosomal copy number changes directly in thin-layer cervical cytology slides by fluorescence in situ hybridization. The probe set consists of a BAC contig that contains sequences for the RNA component of the human telomerase gene (TERC) on chromosome band 3q26, and repeat sequences specific for the centromeres of chromosomes 3 and 7 as controls. in a blinded study, we analyzed 57 thin-layer slides that had been rigorously screened and classified as normal (n = 13), atypical squamous cells (ASC, n = 5), low-grade squamous intraepithelial lesions (LSIL, n = 14), and high-grade squamous intraepithelial lesions (HSM) grade 2 (CIN2, n = 8), and grade 3 (CIN3, n = 17). The percentage of tetraploid cells (P-Trend < 0.0005) and cells with multiple 3q signals increased with the severity of the cytologic interpretation (P-Trend < 0.0005). While only few normal samples, ASC and LSIL lesions, revealed copy number increases of 3q, 63% of the HSIL (CIN2) lesions and 76% of the HSIL (CIN3) lesions showed extra copies of 3q. We conclude that the visualization of chromosome 3q copy numbers in routinely prepared cytological material using BAC clones specific for TERC serves as an independent screening test for HSIL and may help to determine the progressive potential of individual lesions.