Loss of Heterozygosity at the Human RAP1A/Krev-1 Locus Is a Rare Event in Colorectal Tumors

Abstract Kirsten- ras -revertant-1 (K rev -1/Rap1A) is a recently identified tumor suppressor gene which induces flat revertants when introduced into a variety of ras -transformed cell lines in vitro . Since 47% of colorectal carcinomas have transforming mutations in ras protooncogenes, and since K rev -1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the K rev -1 locus may be necessary for transformation of colonic cells. Loss of heterozygosity is a common method of inactivation of tumor suppressor genes in colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients with sporadic colorectal cancer. Because K rev -1 had no previously described polymorphisms, we first identified a Bcl I restriction fragment length polymorphism which showed 40% heterozygosity in 50 unrelated individuals. However, only one tumor from 18 informative patients showed allelic loss at the K rev -1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the K rev -1 locus in colorectal cancer. However, the results do not exclude a role for K rev -1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.