GENOMIC INSTABILITY IN COLORECTAL-CANCER - RELATIONSHIP TO CLINICOPATHOLOGICAL VARIABLES AND FAMILY HISTORY

Recent reports have suggested that one or more genes may cause replica tion errors (RER) during colorectal tumorigenesis. Additional alleles are seen in the tumors when analyzing random microsatellite loci. We h ave studied seven dinucleotide repeat loci, located on seven different chromosomes, by use of polymerase chain reaction amplification and de naturing polyacrylamide gel electrophoresis. We found that 16.5% (40 o f 243) colorectal cancers showed RER at one or several loci (RER+). Th is includes 31% (4 of 13) among cases with a strong positive family hi story according to previously published criteria and 17% (35 of 207) a mong cases with no history of familial cancer. Interestingly, no signi ficant association was found between RER+ tumors and a general familia l clustering of cancer. Microsatellite instability was significantly a ssociated with DNA diploid status of the tumor (P < 0.001), with the l ocation of the tumor in the proximal colon (P < 0.001), and with poorl y differentiated tumor phenotype (P < 0.001). Patients with RER+ at gr eater-than-or-equal-to 2 loci tumors had an increased survival (P = 0. 05). We further analyzed 84 breast cancers and 86 male germ cell cance rs using the same seven markers. None of the tumors were RER+, indicat ing that this phenomenon may be specific to certain types of tumors.