ALLELOTYPE PROFILES OF LOCAL RECURRENCES AND DISTANT METASTASES FROM COLORECTAL-CANCER PATIENTS

Several genetic alterations have been described in benign and malignan t primary tumors of the colorectum, but few such associations have bee n made with the progression of these tumors. This study compares genet ic changes found in distant metastases (n = 22) with local recurrences (n = 15) as well as with primary carcinomas (n = 12). Complete allelo types of the tumors were obtained by analyzing 43 microsatellite loci, representing all non-acrocentric chromosome arms and mapping to the m id-portion of the arms. Allelic imbalances in the tumor DNA were evalu ated by comparison with the patient's constitutional pattern in blood DNA. The allelotype profile of the distant metastases was different fr om those found in the local recurrences and in the primary carcinomas. More than 20% of the distant metastases exhibited allelic imbalances at loci representing 20 chromosome arms. The majority of these regions were less frequently changed in the local recurrences and in the prim ary tumors. The markers that most often were altered in the metastasis (>40%) represented chromosome arms 14q, 17p, 18p and 18q. Only two re gions, 10p and 19p, were unaltered in all tumors analyzed. We found th at the median value of fractional allelic imbalance was twice as high in the distant metastases as in the recurrent tumors. Novel alleles at microsatellite loci were observed in all 3 tumor types, but in the ad vanced tumors this phenotype was characterized by only a single novel allele seen at less than 10% of the analyzed loci. (C) 1996 Wiley-Liss , Inc.