Tracking recurrent quantitative genomic alterations in colorectal cancer: allelic losses in chromosome 4 correlate with tumor aggressiveness

Abstract

Allelic imbalances are common events in cancer cells. Quantitative alterations in specific chromosomal loci have been linked to activation (gain) or inactivation (loss) of genes with a proven impact on tumor cell biology. The aim of this study was to detect new chromosomal regions recurrently altered in colorectal tumorigenesis and with a potential effect on patient's outcome. We have analyzed a series of human colorectal tumor biopsy specimens by using the DNA fingerprinting technique arbitrarily primed PCR. This approach provided information on 95 different loci randomly selected and distributed through out the cell's genome. Eight sequences displayed recurrent alterations associated with diminished patient survival. Four of them (showing allelic losses) were located in chromosome 4, one sequence in chromosome 2, and one sequence in chromosome 17. The chromosomal origin of the two remaining sequences could not be determined. Fine mapping of chromosome 4 bands suggested that there are at least two regions in chromosome 4 (4p14-16 and 4q21-28) susceptible to containing tumor suppressor genes the loss of which may affect tumor aggressiveness.