title: Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene.
abstract: Point mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population-based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor-tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3' UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ-line. Frequencies of the 500 C-->G and 540 C-->T polymorphisms in the 3' UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor-specific survival was significantly shorter in patients with either the 500 C-->G or 540 C-->T polymorphism than those with wild-type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.
authors.affiliation: Department of Biosciences, Karolinska Institute, Huddinge, Sweden.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Petra
authors.initials: P
authors.lastname: Berggren
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steineck
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.forename: Erik
authors.initials: E
authors.lastname: Onelöv
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Per
authors.initials: P
authors.lastname: Larsson
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D019942:Genes, p16; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins