title: Identification of novel genetic alterations in samples of malignant glioma patients.
abstract: Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.
authors.affiliation: University of Belgrade, Institute for Biological Research "Sinisa Stankovic", Department of Neurobiology, Belgrade, Republic of Serbia.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Milinkovic
authors.affiliation: University of Belgrade, Institute for Biological Research "Sinisa Stankovic", Department of Neurobiology, Belgrade, Republic of Serbia.
authors.forename: Jasna
authors.initials: J
authors.lastname: Bankovic
authors.affiliation: Clinical Center of Serbia, Clinic for Neurosurgery, Belgrade, Republic of Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Rakic
authors.affiliation: University of Belgrade, Institute for Biological Research "Sinisa Stankovic", Department of Neurobiology, Belgrade, Republic of Serbia.
authors.forename: Tijana
authors.initials: T
authors.lastname: Stankovic
authors.affiliation: University of Belgrade, School of Medicine, Institute of Pathology, Belgrade, Republic of Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Skender-Gazibara
authors.affiliation: University of Belgrade, Institute for Biological Research "Sinisa Stankovic", Department of Neurobiology, Belgrade, Republic of Serbia.
authors.forename: Sabera
authors.initials: S
authors.lastname: Ruzdijic
authors.affiliation: University of Belgrade, Institute for Biological Research "Sinisa Stankovic", Department of Neurobiology, Belgrade, Republic of Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Tanic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D042822:Genomic Instability; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult