Rare alleles at different VNTR loci among lung-cancer patients with microsatellite instability in tumours.
Work in our laboratory has shown a significantly higher frequency of microsatellite mutations in tumours from lung-cancer patients with rare alleles at the HrasI VNTR locus compared with those with common alleles. In 137 lung-cancer patients, the association between microsatellite instability and rare alleles at the HrasI VNTR locus was confirmed with 17 microsatellite markers. We found a significant association between LOH in lung tumours of marker D3s966 with microsatellite instability. In samples with LOH at marker D3s966 (3p21.3) 22% of loci tested showed instability, whereas 8% showed instability without LOH at D3s966. To investigate whether rare alleles at the HrasI locus are linked to rare alleles at other loci, a second minisatellite (D17S4) was genotyped. In a population of 406, 4 individuals with D 17S4 rare alleles were detected of whom 3 also had rare alleles at the HrasI VNTR locus. The probability of this association to occur by chance is low. Thus, rare alleles at the HrasI locus may be associated with rare alleles at other loci, and could be an indication of germline instability. The findings indicate that microsatellite instability in lung tumours is not strictly associated with features in the HrasI proto-oncogene, but may be the result of the same mechanism(s) that generate(s) new alleles at the HrasI and D17S4 loci.
Lindstedt
B A
BA
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway. bjorn.a.lindstedt@stami.no
Ryberg
D
D
Haugen
A
A
D000483:Alleles; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D018598:Minisatellite Repeats / Q000235:genetics*; D000090063:Proto-Oncogene Mas
D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas