title: Absence of detectable alterations in the putative tumor suppressor gene BTRC in cerebellar medulloblastomas and cutaneous basal cell carcinomas.
abstract: The sonic hedgehog signal transduction pathway is aberrantly activated in the majority of cutaneous basal cell carcinomas and a subset of cerebellar medulloblastomas. The latter tumors may also show activation of the wingless (Wnt) signaling pathway. In Drosophila, the F-box/WD40-repeat containing protein Slimb has been shown to function as an intracellular negative regulator of both pathways. The BTRC gene (beta-transducin repeat-containing protein) is a human homolog of Slimb that is located at 10q24.3, a chromosome region frequently deleted in medulloblastomas. Here, we report on the mutational analysis of BTRC in 91 human tumors, including 66 primitive neuroectodermal tumors (PNETs) of the central nervous system (62 medulloblastomas and 4 supratentorial PNETs) and 25 cutaneous basal cell carcinomas (BCCs). These analyses revealed no tumor-associated BTRC mutations. BTRC transcripts were expressed in non-neoplastic brain tissue, normal skin, as well as in all PNETs and BCCs analyzed by real-time reverse transcription-PCR. Two novel BTRC transcript variants were expressed at higher levels in non-neoplastic brain tissue than in normal skin and the investigated tumors. Taken together, our results indicate that PNETs and BCCs neither show mutations nor loss of mRNA expression of BTRC. Therefore, BTRC alteration does not appear to be involved in the pathogenesis of these neoplasms.
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: Marietta
authors.initials: M
authors.lastname: Wolter
authors.forename: Christian
authors.initials: C
authors.lastname: Scharwächter
authors.forename: Julia
authors.initials: J
authors.lastname: Reifenberger
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
mesh_terms: D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002528:Cerebellar Neoplasms / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics*; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012878:Skin Neoplasms / Q000235:genetics*; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics*
chemical_list: C471644:BTRC protein, human; D012333:RNA, Messenger; D044844:beta-Transducin Repeat-Containing Proteins; D012313:RNA; D004247:DNA