Wainwright L J, Middleton P G, Rees J L
Department of Dermatology, University of Newcastle upon Tyne, Royal Victoria Infirmary, United Kingdom.
Genes Chromosomes Cancer. 1995 Jan;12(1):45-9. doi: 10.1002/gcc.2870120108.
Human telomeres consist of arrays of the sequence TTAGGG up to 15-20 kb in length, which are essential for the maintenance of normal chromosomal stability. It has been suggested that genomic instability observed in tumours may be due to loss of telomere sequences. Somatic cells that are dividing continuously appear to progressively lose telomere sequences, and it would therefore be anticipated that cell type specific differences in mean telomere length may exist within an individual. Previous reports have suggested that mean telomere length may be different in human neoplasia when compared to control. Basal cell carcinomas are epidermal derived tumours and in order therefore to make valid cell type specific comparisons we have measured mean telomere length in 20 basal cell carcinomas as well as in both adjacent epidermis and dermis. Mean telomere length was significantly reduced in epidermis in comparison with dermis, from clinically normal skin immediately adjacent to the tumours (mean difference 2.5 kb). This result is not related to the presence of the tumour as similar results were obtained from skin samples of healthy volunteers. Basal cell carcinomas showed increased mean telomere length in 13/20 samples in comparison with matched epidermis (mean difference 3.1 kb), whereas in 7/20 mean telomere length was reduced (mean difference 2.2 kb). These results showing that mean telomere length varies from cell type to cell type underpin the importance of performing cell type specific controls when assessing changes in tumour telomeres.
人类端粒由长度达15 - 20 kb的TTAGGG序列阵列组成,这对于维持正常染色体稳定性至关重要。有人提出,肿瘤中观察到的基因组不稳定性可能是由于端粒序列的丢失。持续分裂的体细胞似乎会逐渐丢失端粒序列,因此可以预期个体内可能存在细胞类型特异性的平均端粒长度差异。先前的报告表明,与对照相比,人类肿瘤中的平均端粒长度可能不同。基底细胞癌是源自表皮的肿瘤,因此为了进行有效的细胞类型特异性比较,我们测量了20例基底细胞癌以及相邻表皮和真皮中的平均端粒长度。与真皮相比,紧邻肿瘤的临床正常皮肤的表皮中平均端粒长度显著缩短(平均差异2.5 kb)。这一结果与肿瘤的存在无关,因为从健康志愿者的皮肤样本中也获得了类似结果。与匹配的表皮相比,13/20的基底细胞癌样本中平均端粒长度增加(平均差异3.1 kb),而7/20的样本中平均端粒长度缩短(平均差异2.2 kb)。这些结果表明平均端粒长度因细胞类型而异,这突出了在评估肿瘤端粒变化时进行细胞类型特异性对照的重要性。