Detection of HPV and Human Chromosome Sites by Dual-Color Fluorescence In Situ Hybridization Reveals Recurrent HPV Integration Sites and Heterogeneity in Cervical Cancer.
Detection of HPV and Human Chromosome Sites by Dual-Color Fluorescence In Situ Hybridization Reveals Recurrent HPV Integration Sites and Heterogeneity in Cervical Cancer.
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通过双色荧光原位杂交检测 HPV 和人类染色体位点，揭示宫颈癌中复发性 HPV 整合位点和异质性
DOI：
10.3389/fonc.2021.734758
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Xiong J;Cheng J;Shen H;Ren C;Wang L;Gao C;Zhu T;Li X;Ding W;Zhu D;Wang H
人乳头瘤病毒（HPV）整合到人类基因组中被认为是宫颈癌的一个重要病因。随着测序技术的发展，越来越多的整合“热点”被确定。然而，这些HPV整合信息是从对整个宫颈癌组织的分析中得出的，我们对不同癌细胞亚群或单个癌细胞中的整合情况知之甚少。本研究优化了探针的制备，并提供了一种双色荧光原位杂交（FISH）方法来检测石蜡包埋的宫颈癌样本中的HPV整合位点。我们同时使用了HPV探针和位点特异性探针：3p14（FHIT）、8q24（MYC）、13q22（KLF5/KLF12）、3q28（TP63）和5p15（TERT）。我们在96例宫颈癌中的75例中检测到了HPV信号；62例显示点状信号，13例显示弥漫性点状信号。我们在4例宫颈癌中确定3p14为高频HPV整合位点。8p14处的HPV整合发生在2例宫颈癌中。在1321号样本的同一宫颈癌组织中，根据HPV探针观察到两个不同的细胞亚群，但在细胞和细胞核形态上没有差异。我们的研究提供了一种研究宫颈癌中常见HPV整合位点的新方法，并从HPV整合的角度报告了宫颈癌内部的异质性。
Human papillomavirus (HPV) integration in the human genome is suggested to be an important cause of cervical cancer. With the development of sequencing technologies, an increasing number of integration “hotspots” have been identified. However, this HPV integration information was derived from analysis of whole cervical cancer tissue, and we know very little about the integration in different cancer cell subgroups or individual cancer cells. This study optimized the preparation of probes and provided a dual-color fluorescence in situ hybridization (FISH) method to detect HPV integration sites in paraffin-embedded cervical cancer samples. We used both HPV probes and site-specific probes: 3p14 (FHIT), 8q24 (MYC), 13q22 (KLF5/KLF12), 3q28 (TP63), and 5p15 (TERT). We detected HPV signals in 75 of the 96 cases of cervical cancer; 62 cases showed punctate signals, and 13 cases showed diffuse punctate signals. We identified 3p14 as a high-frequency HPV integration site in 4 cervical cancer cases. HPV integration at 8p14 occurred in 2 cases of cervical cancer. In the same cervical cancer tissue of sample No.1321, two distinct subgroups of cells were observed based on the HPV probe but showed no difference in cell and nucleus morphology. Our study provides a new method to investigate the frequent HPV integration sites in cervical cancer and reports the heterogeneity within cervical cancer from the perspective of HPV integration.
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影响因子：
6.4
作者：
Schmitz, Martina;Driesch, Corina;Duerst, Matthias
通讯作者：
Duerst, Matthias
影响因子：
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Van Tine, BA;Kappes, JC;Chow, LT
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Chow, LT
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Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
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Chinnaiyan, AM
影响因子：
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Melsheimer, P;Vinokurova, S;Doeberitz, MV
通讯作者：
Doeberitz, MV
影响因子：
6.4
作者：
Hopman, AHN;Kamps, MA;Ramaekers, FCS
通讯作者：
Ramaekers, FCS