Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors.
Kirsten-ras-revertant-1 (Krev-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 Krev-1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the Krev-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 Krev-1 had no previously described polymorphisms, we first identified a BclI 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 Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the Krev-1 locus in colorectal cancer. However, the results do not exclude a role for Krev-1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.
Young
J
J
Queensland Cancer Fund Research Unit, Joint Oncology Program, Queensland Institute of Medical Research, Herston, Australia.
Searle
J
J
Stitz
R
R
Cowen
A
A
Ward
M
M
Chenevix-French
G
G
D000469:Alkaline Phosphatase / Q000235:genetics; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D015179:Colorectal Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D012083:Renin / Q000235:genetics
D005819:Genetic Markers; D000469:Alkaline Phosphatase; D012083:Renin