Telomere DNA content and allelic imbalance demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

Christopher M. Heaphy, Marco Bisoffi, Colleen A. Fordyce, Christina M. Haaland, William C. Hines, Nancy E. Joste, Jeffrey K. Griffith

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)108-116
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number1
DOIs
StatePublished - Jul 1 2006

Keywords

  • Allelic imbalance
  • Breast cancer
  • Cancer field effect
  • Genomic instability
  • Telomere loss

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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