In situ analyses of genome instability in breast cancer.
Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer. We modeled this process in vitro by measuring these same features in human mammary epithelial cell cultures during ZNF217-mediated transition through telomere crisis and immortalization. Taken together, the data suggest that transition through telomere crisis and immortalization in breast cancer occurs during progression from usual ductal hyperplasia to ductal carcinoma in situ.
Department of Laboratory Medicine and Comprehensive Cancer Center, University of California San Francisco, California, USA.
Koei
K
Chin
Carlos Ortiz
CO
de Solorzano
David
D
Knowles
Arthur
A
Jones
William
W
Chou
Enrique Garcia
EG
Rodriguez
Wen-Lin
WL
Kuo
Britt-Marie
BM
Ljung
Karen
K
Chew
Kenneth
K
Myambo
Monica
M
Miranda
Sheryl
S
Krig
James
J
Garbe
Martha
M
Stampfer
Paul
P
Yaswen
Joe W
JW
Gray
Stephen J
SJ
Lockett
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D043171:Chromosomal Instability; D018450:Disease Progression; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D017403:In Situ Hybridization; D016615:Telomere / Q000000981:diagnostic imaging*; D014407:Tumor Cells, Cultured; D014463:Ultrasonography