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

Allelic imbalances are common events in cancer cells. Quantitative alterati ons in specific chromosomal loci have been linked to activation (gain) or i nactivation (loss) of genes with a proven impact on tumor cell biology. The aim of this study was to detect new chromosomal regions recurrently altere d in colorectal tumorigenesis and with a potential effect on patient's outc ome. We have analyzed a series of human colorectal tumor biopsy specimens b y using the DNA fingerprinting technique arbitrarily primed PCR. This appro ach provided information on 95 different loci randomly selected and distrib uted through out the cell's genome. Eight sequences displayed recurrent alt erations 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 rema ining 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 whic h may affect tumor aggressiveness.