MUTATIONS OF E2F-4 TRINUCLEOTIDE REPEATS IN COLORECTAL-CANCER WITH MICROSATELLITE INSTABILITY

Genetic instability at microsatellites in some colorectal cancer (CRC) have been linked to the defects of human mismatch repair genes, but t he targets of these defective genes have been largely unknown. We scre ened CRC specimens for alteration of E2F-4 gene by analyzing both cDNA and genomic sequences along with replication error (RER(+)) phenotype . Two out of 20 sporadic CRC patients showed RER(+) phenotype. We foun d tumor-specific copy number alteration in 13 consecutive trinucleotid e (GAG) repeats within the coding exon of E2F-4 exclusively in these 2 specimens. Thus, E2F-4 may be a clue of the target gene of defective repair genes in CRC with genetic instability in addition to the TGF-be ta type II receptor gene. (C) 1996 Academic Press, Inc.