title: Giant subependymoma developed in a patient with aniridia: analyses of PAX6 and tumor-relevant genes.
abstract: We observed an unusually large subependymoma in a female patient with congenital aniridia. To analyze the genetic mechanisms of tumorigenesis, we first examined the paired box 6 (PAX6) gene using both tumor tissue and peripheral lymphocytes. Tumor suppressor activity has been proposed for PAX6 in gliomas, in addition to its well-known role in the eye development. Using genomic quantitative PCR and loss of heterozygosity analysis, we identified hemizygous deletions in the 5'-region of PAX6. In lymphocytes, the deletion within PAX6 spanned from between exons 6 and 7 to the 5'-upstream region of the gene, but did not reach the upstream gene, RNC1, which is reported to be associated with tumors. The subependymoma had an additional de novo deletion spanning from the intron 4 to intron 6 of PAX6, although we could not completely determine whether these two deletions are on the same chromosome or not. We also examined other potentially relevant tumor suppressor genes: PTEN, TP53 and SOX2. However, we detected no exonic mutations or deletions in these genes. Collectively, we speculate that the defect in PAX6 may have contributed to the extremely large size of the subependymoma, due to a loss of tumor suppressor activity in glial cell lineage.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako-city, Saitama, Japan. mmaekawa@brain.riken.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Akira
authors.initials: A
authors.lastname: Tamase
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D015783:Aniridia / Q000150:complications; D001254:Astrocytoma / Q000209:etiology / Q000235:genetics*; D001932:Brain Neoplasms / Q000209:etiology / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins