title: Multiplex ligation-dependent probe amplification: a diagnostic tool for simultaneous identification of different genetic markers in glial tumors.
abstract: Genetic aberrations in tumors are predictive for chemosensitivity and survival. A test is needed that allows simultaneous detection of multiple changes and that is widely applicable in a routine diagnostic setting. Multiplex ligation-dependent probe amplification (MLPA) allows detection of DNA copy number changes of up to 45 loci in one relatively simple, semiquantitative polymerase chain reaction-based assay. To assess the applicability of MLPA, we performed MLPA analysis to detect relevant genetic markers in a spectrum of 88 gliomas. The vast majority of these tumors (n = 79) were previously characterized by comparative genomic hybridization. With MLPA kit P088 (78 cases), complete and partial loss of 1p and 19q were reliably identified, even in samples containing only 50% tumor DNA. Distinct 1p deletions exist with different clinically prognostic consequences, and in contrast to the commonly used diagnostic strategies (loss of heterozygosity or fluorescent in situ hybridization 1p36), P088 allows detection of such distinct 1p losses. Combining P088 with P105 will further increase the accurate prediction of clinical behavior because this kit identified markers (EGFR, PTEN, and CDKN2A) of high-grade malignancy in 41 cases analyzed. We conclude that MLPA is a reliable diagnostic tool for simultaneous identification of different region-specific genetic aberrations of tumors.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. j.jeuken@pathol.umcn.nl
authors.forename: Judith
authors.initials: J
authors.lastname: Jeuken
authors.forename: Sandra
authors.initials: S
authors.lastname: Cornelissen
authors.forename: Sandra
authors.initials: S
authors.lastname: Boots-Sprenger
authors.forename: Sabine
authors.initials: S
authors.lastname: Gijsen
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
mesh_terms: D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D005819:Genetic Markers; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D009693:Nucleic Acid Hybridization; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D005819:Genetic Markers; D011933:Reagent Kits, Diagnostic