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

• Published in: International journal of cancer Vol. 119; no. 1; pp. 108 - 116
• Main Authors: Heaphy, Christopher M., Bisoffi, Marco, Fordyce, Colleen A., Haaland, Christina M., Hines, William C., Joste, Nancy E., Griffith, Jeffrey K.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-07-2006; Wiley-Liss
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allelic Imbalance; Biological and medical sciences; Breast - chemistry; Breast - pathology; breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - genetics; Breast Neoplasms - pathology; cancer field effect; Cell Transformation, Neoplastic - genetics; DNA, Neoplasm - analysis; Female; Genomic Instability; Gynecology. Andrology. Obstetrics; Humans; Male; Mammary gland diseases; Medical sciences; Middle Aged; Precancerous Conditions - genetics; Telomere - genetics; telomere loss; Tumors; Human; cancer field effect; Allelic imbalance; Breast cancer; Malignant tumor; Genetic instability; Telomere; Mammary gland diseases; Cancerology; DNA; Genetics; Genome; genomic instability; telomere loss; Field cancerization
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21815

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.