Genomic instability demonstrates similarity between DCIS and invasive carcinomas
Purpose To assess telomere DNA content (TC) and the number of sites of allelic imbalance (AI) as a function of breast cancer progression. Experimental design TC and AI were determined in 54 histologically normal tissues, 10 atypical ductal hyperplasias (ADH), 122 in situ ductal carcinomas (DCIS) and 535 invasive carcinomas (Stage I–IIIA). Results TC was altered in ADH lesions (20%), DCIS specimens (53%) and invasive carcinomas (51%). The mean number of sites of AI was 0.26 in histologically normal group tissue, increased to 1.00 in ADH, 2.94 in DCIS, and 3.07 in invasive carcinomas. All groups were statistically different from the histologically normal group (P < 0.001 for each); however, there was no difference between DCIS and the invasive groups. Conclusions Genomic instability increases in ADH and plateaus in DCIS without further increase in the invasive carcinomas, supporting the notion that invasive carcinomas evolve from or in parallel with DCIS.
KeywordsAllelic imbalance Breast cancer Ductal carcinoma in situ Genomic instability Telomere DNA content
This work was supported by grants DAMD17-01-1-0572, W81XWH-05-1-0226, W81XWH-05-1-0273 from the DOD Breast Cancer Research Program, NO-1-CN-65034-29 and SEER, NCI-PC-05016-20 from NCI/SEER and RR0164880 from the NIH. We thank Terry Mulcahy and Phillip Enriquez III from DNA Research Services of the University of New Mexico Health Sciences Center for gel capillary analysis.
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