title: Alterations of the INK4a/ARF locus in human intracranial germ cell tumors.
abstract: Little is known about the molecular mechanisms responsible for the development of intracranial germ cell tumors (ICGTs). Recently, we demonstrated that the balance of the p53-mdm2 interactions is disrupted in ICGTs. The p14ARF product, a tumor suppresser gene located on the INK4a/ARF locus, acts as one of the major factors affecting p53-mdm2 interactions via its binding to mdm2 and the stimulation of mdm2 degradation. To evaluate whether genetic alterations of the INK4a/ARF locus occur in the genesis of ICGTs, we analyzed the INK4a/ARF genes in 21 ICGTs-10 pure germinomas and 11 nongerminomatous germ cell tumors. Fifteen (71%) of the 21 ICGTs displayed genetic alterations, including 14 homozygous deletions and 1 frameshift mutation. Furthermore, the frequency of the alterations was higher in pure germinomas [9 (90%) of the 10] than in nongerminomatous germ cell tumors [6 (55%) of the 11; P = 0.09]. These data suggested that INK4a/ARF gene abnormalities could play an important role in the genesis of ICGTs, especially in pure germinoma.
authors.affiliation: Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwato
authors.forename: O
authors.initials: O
authors.lastname: Tachibana
authors.forename: Y
authors.initials: Y
authors.lastname: Tohma
authors.forename: Y
authors.initials: Y
authors.lastname: Arakawa
authors.forename: H
authors.initials: H
authors.lastname: Nitta
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: J
authors.initials: J
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D018237:Germinoma / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF