High frequency of mutations in the PIK3CA gene helical and kinase coding regions in a group of Iranian patients with high-grade glioblastomas: five novel mutations.
Glioblastoma multiform (GBM; World Health Organization (WHO) grade IV) and anaplastic astrocytomas (AA; WHO grade III) are highly aggressive and lethal astrocytic brain tumors. To detect cancer-specific somatic mutations in two hot-spot regions of PIK3CA gene, the helical and kinase domains (encoded by exons 9 and 20, respectively) in GBM and AA, the authors examined the respective sequences 31 paraffin-embedded samples (23 GBM and 8 AA). The samples were obtained from a group of Iranian patients affected with high-grade glioblastoma (HGG). The overall prevalence of PIK3CA mutations was 23% (7/31) for both tumor types (22% in GBM, and 25% in AA). Five mutations were detected in exon 20, p.Arg992Gln (c.2976G→A), p.Met1005Val (c.3014A→G), p.Ile1019→Val (c.3056A→G), p.Ser1008Cys (c.3024C→G), and p.Asn1044Asp (c.3130A→G), and one mutation in exon 9, p.Glu545Ala (c.1634A→C). Additionally exons 4-8 of P53 gene in four unrelated young patients, who showed no mutations in PIK3CA exons 9 and 20, were analyzed. Three mutations were identified: p.Pro72Ala (c.214C→G), g.11608G→T (homozygote splice mutation), and p.Thr170Thr (c.510G→A silent mutation). In conclusion, mutation detection in PIK3CA in patients with a high degree of malignancy and early age at diagnosis should be included in molecular diagnostic protocols, also with regard to possible upcoming therapies.
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran. derakhshandeh@tums.ac.ir
Pupak
P
Derakhshandeh-Peykar
Jalil
J
Alivi
Arash
A
Hossein-nezhad
Arash
A
Hosseinnejad
Bernd
B
Rautenstrauss
Reza Ebrahimzadeh
RE
Vesal
Afsoon
A
Doriani
D017668:Age of Onset; D001932:Brain Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005909:Glioblastoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016366:Open Reading Frames / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human