title: Impact of novel PTEN mutations in Turkish patients with glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) represents the most common and aggressive type of primary neoplasms of the central nervous system. The PTEN (phosphatase, tensin homologue, deleted on chromosome TEN; MIM # 601728) tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds and because there is no study evaluating PTEN mutation in Turkish patients with GBM, we aimed to realize the present study. We investigated 62 GBM tumors for mutations of the PTEN gene using single strand conformational polymorphism (SSCP) method followed by DNA sequencing. As a result of our investigation, PTEN mutations were detected in 15 of 62 tumors (24.19%). Nine different sequence variants were identified: one novel promoter site mutation (5'UTR -9C-->T), one novel intronic mutation (IVS2-2delA), four novel point mutations (61A-->G, 105T-->G, 248C-->G, and 364C-->G), two novel frameshift mutations (213delC) and 378delGATA) and one previously reported global exonic transition type mutation (129G-->A). Since the majority of PTEN mutations identified in the present study are novel, we believe that these alterations may be specific to Turkish population. Furthermore, though no significant correlation was found between PTEN mutations and histopathological properties of GBM tumors, our findings indicate that localizations of mutations in PTEN gene may have an effect on clinical aggressiveness of GBM tumors.
authors.affiliation: Department of Medical Biology, School of Medicine, Uludag University, Bursa, Turkey. btunca@uludag.edu.tr
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bekar
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.forename: Ozgur
authors.initials: O
authors.lastname: Vatan
authors.forename: Sahsine
authors.initials: S
authors.lastname: Tolunay
authors.forename: Hasan
authors.initials: H
authors.lastname: Kocaeli
authors.forename: Kaya
authors.initials: K
authors.lastname: Aksoy
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D014421:Turkey
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human