PRESENCE AND INSTABILITY OF REPETITIVE ELEMENTS IN SEQUENCES THE ALTERED EXPRESSION OF WHICH CHARACTERIZES RISK FOR COLONIC-CANCER

50C10 and 52H10 are two DNA clones previously reported by us to be ove rexpressed in human colonic mucosa at high risk for development of col onic tumors. This report presents sequencing data that reveal that the se clones contain repetitive Alu elements, Each Alu sequence is associ ated with a 3'-oligoadenylate [oligo(A)] sequence, which is demonstrat ed to exhibit instability in human colonic tumors, The oligo(ii) seque nces only decrease in length, unlike microsatellites, which can either increase or decrease, Rigorous quantitative analysis of the length of the oligo(A) sequence in colonic tumors demonstrates that the standar d deviation of the length of the sequence in tumors is a function of t he mean length; i.e,, as the oligo(A) sequence becomes progressively s horter, the variance increases. Both measurements, therefore, provide a quantitative index of the extent of instability in a tissue, Compari son of instability at the oligo(A) loci defined by 50C10 and 52H10 to instability at a CA microsatellite upstream of the apoD gene, and comp arison of an oligo(ii) and a CA microsatellite both in the 3' untransl ated region of the cyclin D1 mRNA demonstrate that instability in a tu mor, when present, is more prominent for the oligo(A) sequences than f or the microsatellite (P < 0.0001), This suggests either that the mech anisms that generate oligo(A) instability are more penetrant than thos e that generate microsatellite instability, or that the instability at oligo(A) sequences takes place earlier in the development of the tumo r and is selected for, thus becoming more prominent. These features of oligo(A) instability suggest that they may be uniquely useful in dete cting and quantifying instability in tissues. Further, the presence of repetitive sequence elements in loci overexpressed in colonic mucosa at risk may be related to an extensive Literature that demonstrates th at a variety of repetitive sequences accumulate in the cellular RNA po pulation during carcinogenesis and in tumors, Such RNA sequences could play a mechanistic role in tumor development.