title: KRAS mutation screening by chip-based DNA hybridization--a further step towards personalized oncology.
abstract: The use of predictive biomarkers can help to improve therapeutic options for the individual cancer patient. For the treatment of colon cancer patients with anti-EGFR-based drugs, the KRAS mutation status has to be determined to pre-select responders that will benefit from this medication. Amongst others, array-based tests have been established for profiling of the KRAS mutation status. Within this article we describe an on-chip hybridization technique to screen therapeutic relevant KRAS codon 12 mutations. The DNA chip-based platform enables the reliable discrimination of selected mutations by allele-specific hybridization. Here, silver deposits represent robust endpoint signals that allow for a simple naked eye rating. With the here presented assay concept a precise identification of heterozygous and homozygous KRAS mutations, even against a background of up to 95% wild-type DNA, was realizable. The applicability of the test was successfully proven for various cancer cell lines as well as clinical tumour samples. Thus, the chip-based DNA hybridization technique seems to be a promising tool for KRAS mutation analysis to further improve personalized cancer treatment.
authors.affiliation: Leibniz Institute of Photonic Technology Jena, Albert-Einstein-Str. 9, 07745 Jena, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Steinbach
authors.forename: Carolin
authors.initials: C
authors.lastname: Steinbrücker
authors.forename: Sibyll
authors.initials: S
authors.lastname: Pollok
authors.forename: Katharina
authors.initials: K
authors.lastname: Walther
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Clement
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
authors.forename: Dana
authors.initials: D
authors.lastname: Cialla-May
authors.forename: Karina
authors.initials: K
authors.lastname: Weber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Popp
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D003062:Codon / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012834:Silver / Q000737:chemistry
chemical_list: D003062:Codon; C117307:KRAS protein, human; D012834:Silver; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)