Telomere DNA content and allelic imbalance demonstrate field cancerization in histologically normal tissue adjacent to breast tumors
Christopher M. Heaphy
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorMarco Bisoffi
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorColleen A. Fordyce
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorChristina M. Haaland
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorWilliam C. Hines
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorNancy E. Joste
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorCorresponding Author
Jeffrey K. Griffith
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Fax: +1-505-272-6587
Department of Biochemistry and Molecular Biology, MSC08 4670, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USASearch for more papers by this authorChristopher M. Heaphy
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorMarco Bisoffi
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorColleen A. Fordyce
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorChristina M. Haaland
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorWilliam C. Hines
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorNancy E. Joste
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Search for more papers by this authorCorresponding Author
Jeffrey K. Griffith
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA
Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
Fax: +1-505-272-6587
Department of Biochemistry and Molecular Biology, MSC08 4670, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USASearch for more papers by this authorAbstract
Cancer arises from an accumulation of mutations that promote the selection of cells with progressively malignant phenotypes. Previous studies have shown that genomic instability, a hallmark of cancer cells, is a driving force in this process. In the present study, two markers of genomic instability, telomere DNA content and allelic imbalance, were examined in two independent cohorts of mammary carcinomas. Altered telomeres and unbalanced allelic loci were present in both tumors and surrounding histologically normal tissues at distances at least 1 cm from the visible tumor margins. Although the extent of these genetic changes decreases as a function of the distance from the visible tumor margin, unbalanced loci are conserved between the surrounding tissues and the tumors, implying cellular clonal evolution. Our results are in agreement with the concepts of “field cancerization” and “cancer field effect,” concepts that were previously introduced to describe areas within tissues consisting of histologically normal, yet genetically aberrant, cells that represent fertile grounds for tumorigenesis. The finding that genomic instability occurs in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it has implications for the definition of appropriate tumor margins and the assessment of recurrence risk factors in the context of breast-sparing surgery. © 2006 Wiley-Liss, Inc.
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