KCTD11 expression in medulloblastoma is lower than in adult cerebellum and higher than in neural stem cells.
Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and the most frequent associated genetic alteration is loss of heterozygosity on chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and HIC1, have been proposed as involved in MB pathogenesis. We used real-time polymerase chain reaction in 20 tissue samples of primary MB to examine the transcriptional level of the two genes, with reference to two types of controls: adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11 expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of MB samples. Neural stem cells had even lower levels of KCTD11 expression than did MB. HIC1 gene expression was low ( approximately 100 times lower than KCTD11 expression) in MB, and low also in both adult cerebellum and neural stem cells. Hypermethylation of the 5'UTR or the central region of HIC1 (or both) was detected in a significant number of MB samples, as well as in cerebellum and neural stem cells. Our data suggest that KCTD11 may play an important role in MB tumorigenesis, but do not support the role of HIC1 in this tumor development. We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control.
Zawlik
Izabela
I
Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland. izazawlik@yahoo.com
Zakrzewska
Magdalena
M
Witusik
Monika
M
Golanska
Ewa
E
Kulczycka-Wojdala
Dominika
D
Szybka
Malgorzata
M
Piaskowski
Sylwester
S
Wozniak
Krystyna
K
Zakrzewski
Krzysztof
K
Papierz
Wielislaw
W
Liberski
Pawel P
PP
Rieske
Piotr
P
D000293:Adolescent; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002531:Cerebellum / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014166:Transferases
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D015221:Potassium Channels; D014157:Transcription Factors; C488725:KCTD11 protein, human; D014166:Transferases