title: A simple method of investigating mutations in CHEK2 by DHPLC: a study of the German populations of Saxony, Saxony-Anhalt, and Thuringia.
abstract: Allele variants of the CHEK2 gene have been found to be associated with several types of cancer, including cancer of the breast, prostate, lung, and ovary. In the Polish population, three founder mutations of CHEK2 have been identified: I157T, 444+1G>A (formerly IVS2+1G>A), and 1100delC. The aim of our study was to establish a simple method to identify founder CHEK2 mutations and determine the prevalence of these changes in the population of Eastern Germany (Saxony, Saxony-Anhalt, and Thuringia). We drew up denaturing high-performance liquid chromatography (DHPLC) conditions for analysis of intron 2 and exon 3 for two mutations (444+1G>A, I157T) and exon 10 for mutation 1100delC. We tested 251 patients and controls. Mutations show a similar frequency in the general population of Eastern Germany as in neighboring Poland (4.95% vs. 4.8% for the missense mutation I157T and 0.99% vs. 0.5% for the truncating mutations 444+1G>A and 1100delC). Investigation of these mutations by DHPLC is highly sensitive and less time-consuming compared to restriction fragment length polymorphism or allele-specific oligonucleotide polymerase chain reaction. It can be easily integrated into diagnostic testing.
authors.affiliation: Institute of Human Genetics, University of Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Scharrer
authors.forename: Marzena
authors.initials: M
authors.lastname: Skrzypczak-Zielinska
authors.forename: Weronika
authors.initials: W
authors.lastname: Wituszynska
authors.forename: Marek
authors.initials: M
authors.lastname: Mierzejewski
authors.forename: Kristin
authors.initials: K
authors.lastname: Krause
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Ursula G
authors.initials: UG
authors.lastname: Froster
mesh_terms: D016022:Case-Control Studies; D064447:Checkpoint Kinase 2; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004252:DNA Mutational Analysis; D005828:Genetics, Population / Q000379:methods*; D005858:Germany; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases