Rashid-Kolvear Fariborz, Pintilie Melania, Done Susan J
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Neoplasia. 2007 Apr;9(4):265-70. doi: 10.1593/neo.07106.
It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared normal breast epithelium, duct carcinoma in situ (DCIS), and invasive duct carcinoma (IDC) from 18 patients. Telomere length was specifically measured on chromosome 17q and was found to be shorter in DCIS and IDC than in normal breast epithelial cells, with more heterogeneity in telomere length in DCIS associated with IDC than in DCIS alone. More importantly, we found that the shortening of telomere on chromosome 17q is greater than the average shortening of all telomeres. This finding indicates that telomere shortening is not simply the result of the end replication problem; otherwise, all telomeres should be subjected to the same rate of telomere shortening. It seems there are mechanisms that preferentially erode some telomeres more than others or preferentially protect some chromosome ends. Our results suggest that the increased level of telomere shortening on 17q may be involved in chromosome instability and the progression of DCIS.
已知浸润性乳腺癌的总端粒长度比正常乳腺组织短,但个体端粒长度的状况尚未得到研究。部分困难在于,通常在间期细胞中是对所有染色体的端粒长度一起进行测量。在本研究中,我们比较了18例患者的正常乳腺上皮、原位导管癌(DCIS)和浸润性导管癌(IDC)。专门对17号染色体长臂上的端粒长度进行了测量,发现DCIS和IDC中的端粒长度比正常乳腺上皮细胞中的短,与单纯DCIS相比,DCIS合并IDC时端粒长度的异质性更大。更重要的是,我们发现17号染色体长臂上的端粒缩短程度大于所有端粒的平均缩短程度。这一发现表明,端粒缩短并非仅仅是末端复制问题的结果;否则,所有端粒的缩短速率应该相同。似乎存在一些机制,优先侵蚀某些端粒而非其他端粒,或者优先保护某些染色体末端。我们的结果表明,17号染色体长臂上端粒缩短水平的增加可能与染色体不稳定性及DCIS的进展有关。