title: Detection and assignment of TP53 mutations in tumor DNA using peptide mass signature genotyping.
abstract: This report describes the application of a new approach to tumor genotyping called peptide mass signature genotyping (PMSG) that is particularly suited to detecting minority sequences in a DNA sample. Detecting minority sequences is essential for accurate tumor genotyping because tumor resections are generally a mixture of malignant and non-malignant cells, with the mutations of interest often outnumbered by the corresponding wild-type alleles. To explore the suitability of PMSG for tumor genotyping, 25 human squamous cell carcinomas of the head and neck, as well as a set of cell lines derived from those tumors, were analyzed for mutations in exons 5 to 8 of the TP53 gene, the exons that encode the DNA-binding domains of the p53 protein. PMSG identified mutations in 11 tumor DNA samples, whereas dideoxy sequencing of the same samples detected mutations in only four. Currently, PMSG can be used to detect mutations that are present in only 20% of the sample DNA, and we expect that this threshold will be lowered significantly as the PMSG process is improved. Hum Mutat 22:158-165, 2003.
authors.affiliation: SpectraGenetics, Pittsburgh, Pennsylvania, USA. cheryl.telmer@spectragenetics.com
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Telmer
authors.forename: Jiyan
authors.initials: J
authors.lastname: An
authors.forename: David E
authors.initials: DE
authors.lastname: Malehorn
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zeng
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Gollin
authors.forename: Chandramohan S
authors.initials: CS
authors.lastname: Ishwad
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Jarvik
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010455:Peptides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D010455:Peptides; D016159:Tumor Suppressor Protein p53