Loss of heterozygosity at chromosome 9p21 (INK4-p14ARF locus): homozygous deletions and mutations in the p16 and p14ARF genes in sporadic primary melanomas.
Loss of heterozygosity (LOH) was determined in 45 sporadic primary melanomas at six polymorphic microsatellite markers that flank the INK4a (p16-p14ARF) locus on chromosome 9p21. We also determined allelic loss at two markers on chromosome 9q and two markers at the Rb locus on chromosome 13. Homozygous deletion of the p16 and p14ARF genes was determined by a fluorescent-based quantitative multiplex polymerase chain reaction method. LOH at one or more polymorphic microsatellite markers on locus 9p21 was found in 32 of the melanomas (71%). The highest proportion of LOH was found at markers D9S736 and D9S104, which are telomeric and centromeric to the INK4 locus, respectively. Five melanomas showed LOH at all the analysed markers located on chromosome 9p21. LOH at markers D9S942 and D9S974, which are located close to the p16 and p14ARF genes, was found in 39% and 46% of melanomas, respectively. Analysis of the marker D9S257 on 9q22.1 showed LOH in 13 melanomas (44% of the informative cases). A subset of melanomas with LOH at the INK4 locus also carried inactivating mutations within the p16 coding sequence. Four melanomas carried homozygous deletions at the p16-p14ARF locus. Our results suggest, besides the involvement of the INK4 locus in sporadic melanomas, the possibility of the existence of additional tumour suppressor loci on chromosome 9.
Kumar
R
R
Department of Biosciences, Karolinska Institute, Novum, Huddinge, Sweden. rajiv.kumar@cnt.ki.se
Smeds
J
J
Lundh Rozell
B
B
Hemminki
K
K
D000483:Alleles; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D002899:Chromosomes, Human, Pair 9; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics*; D018895:Microsatellite Repeats; D008957:Models, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF
D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF