title: DNA fingerprinting of glioma cell lines and considerations on similarity measurements.
abstract: Glioma cell lines are an important tool for research in basic and translational neuro-oncology. Documentation of their genetic identity has become a requirement for scientific journals and grant applications to exclude cross-contamination and misidentification that lead to misinterpretation of results. Here, we report the standard 16 marker short tandem repeat (STR) DNA fingerprints for a panel of 39 widely used glioma cell lines as reference. Comparison of the fingerprints among themselves and with the large DSMZ database comprising 9 marker STRs for 2278 cell lines uncovered 3 misidentified cell lines and confirmed previously known cross-contaminations. Furthermore, 2 glioma cell lines exhibited identity scores of 0.8, which is proposed as the cutoff for detecting cross-contamination. Additional characteristics, comprising lack of a B-raf mutation in one line and a similarity score of 1 with the original tumor tissue in the other, excluded a cross-contamination. Subsequent simulation procedures suggested that, when using DNA fingerprints comprising only 9 STR markers, the commonly used similarity score of 0.8 is not sufficiently stringent to unambiguously differentiate the origin. DNA fingerprints are confounded by frequent genetic alterations in cancer cell lines, particularly loss of heterozygosity, that reduce the informativeness of STR markers and, thereby, the overall power for distinction. The similarity score depends on the number of markers measured; thus, more markers or additional cell line characteristics, such as information on specific mutations, may be necessary to clarify the origin.
authors.affiliation: Laboratory of Brain Tumor Biology and Genetics, Department of Clinical Neurosciences, University Center of Legal Medicine, Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bady
authors.forename: Annie-Claire
authors.initials: AC
authors.lastname: Diserens
authors.forename: Vincent
authors.initials: V
authors.lastname: Castella
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kalt
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hamou
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Monika E
authors.initials: ME
authors.lastname: Hegi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm