Evidence for field effect cancerization in colorectal cancer

- To examine evidence of field cancerization in CRC we performed gene expression, CNA and LOH in tumors and adjacent areas.
- Many chromosomal abnormalities in the tumor cells were detected which had been previously reported in colorectal cancer.
- Although not many, some regions of copy number and LOH events were discernable in the cells around the tumors.
- These CNAs were inconsistent across the field in the same patient suggestive of a field of chromosomal instability.
- Our findings support the mutator phenotype models for field cancerization and tumorigenesis in CRC.

We compared transcript expression, and chromosomal changes on a series of tumors and surrounding tissues to determine if there is evidence of field cancerization in colorectal cancer. Epithelial cells were isolated from tumors and areas adjacent to the tumors ranging from 1 to 10 cm. Tumor abnormalities mirrored those previously reported for colon cancer and while the number and size of the chromosomal abnormalities were greatly reduced in cells from surrounding regions, many chromosome abnormalities were discernable. Interestingly, these abnormalities were not consistent across the field in the same patient samples suggesting a field of chromosomal instability surrounding the tumor. A mutator phenotype has been proposed to account for this instability which states that the genotypes of cells within a tumor would not be identical, but would share at least a single mutation in any number of genes, or a selection of genes affecting a specific pathway which provide a proliferative advantage.