Sunpaweravong S, Sunpaweravong P, Sathitruangsak C, Mai S
Genomic Center for Cancer Research and Diagnosis, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand.
Dis Esophagus. 2016 May;29(4):307-13. doi: 10.1111/dote.12317. Epub 2015 Jan 27.
Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P < 0.0001 and P = 0.0078, respectively. There were no statistically significant differences in the numbers of telomere aggregates or the nuclear volumes between the tumor and normal epithelial cells. Secondary analyses examined the effects of age on 3D telomere architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture between the ESCC and normal epithelial tissues. However, there were no differences observed between the young and old patients.
端粒是位于染色体末端的重复核苷酸序列（TTAGGG）n，其功能是保持染色体完整性并防止末端端端融合。端粒丢失或功能障碍会导致断裂-桥接-融合循环、非整倍体、基因扩增和染色体重排，进而导致基因组不稳定并促进癌变。为了评估端粒变化是否有助于食管鳞状细胞癌（ESCC）的发生发展，并确定年轻患者和老年患者之间是否存在差异，我们比较了ESCC肿瘤细胞与来自同一患者的正常上皮细胞的三维（3D）核端粒结构。患者按年龄平均分为两组，一组为年龄小于45岁的患者，另一组为年龄大于80岁的患者。在ESCC患者中，对距离肿瘤边界至少10 cm的肿瘤和正常上皮细胞进行活检。对每个样本进行苏木精和伊红染色，以确认和识别癌细胞和正常上皮细胞。本研究基于定量三维荧光原位杂交（Q-FISH）、三维成像和石蜡包埋切片的三维分析。使用每张载玻片100个细胞核对三维端粒结构数据进行计算机分析。比较的主要参数如下：信号数量（端粒数量）、信号强度（端粒长度）、端粒聚集体数量和核体积。比较了16例患者的肿瘤和正常上皮样本。正常上皮细胞的端粒信号比肿瘤细胞更多，强度更高，P值分别为P < 0.0001和P = 0.0078。肿瘤细胞和正常上皮细胞之间的端粒聚集体数量或核体积没有统计学上的显著差异。二次分析研究了年龄对三维端粒结构的影响，发现在肿瘤细胞或上皮细胞中，年轻患者和老年患者在任何测试参数上均无统计学上的显著差异。三维核端粒特征能够检测ESCC与正常上皮组织之间端粒结构的差异。然而，年轻患者和老年患者之间未观察到差异。
