Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer

Abstract

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.

Figure 1

FISH analysis of breast FFPE sections. (A) Comparable hematoxylin and eosin sections were used to determine regions of interest. (B–D) FISH with subtelomeric DNA probe to label chromosome 17q (orange signals) and pantelomereic PNA probe (green signals) on FFPE sections (original magnification, × 100). Representative images of normal breast epithelial tissue, DCIS, and IDC are shown in each row. DAPI was used as a counterstain. Identical images in black and white shown in (C–D) with nuclei outlined in gray and (C) telomere and (D) subtelomereic chromosome 17q signals represented by the dark spots (indicated by arrows). Note reduction in telomere signal number, intensity, and size in DCIS and IDC compared with normal tissue.

Figure 2

Comparison of the normalized intensities of telomere length between normal breast epithelial tissue, DCIS, and IDC: (A) normalized total telomere length, (B) normalized chromosome 17q telomere length. Note significant reduction in telomere intensity in DCIS and IDC in comparison with normal breast epithelial tissue.

Figure 3

Distribution of telomere length between DCIS and DCIS associated with IDC: (A) normalized total telomere lengths, (B) normalized chromosome 17q telomere lengths. There are no significant differences in telomere length between DCIS and DCIS associated with IDC.