CTNNB1 (beta-catenin) mutation is rare in brain tumours but involved as a sporadic event in a brain metastasis.
BACKGROUND
The Wnt signaling pathway has been implicated in colon and other cancers. Nevertheless, few or no mutations of CTNNB1 (beta-catenin) have so far been described in brain cancer. We therefore examined the prevalence of constitutive activation of the Wnt signaling pathway in brain cancer specimens as well as cancer cell lines.


METHODS
We used polymerase chain reaction PCR and direct sequencing methods to investigate whether mutations in the CTNNB1 phosphorylation sites S33, S37, S41 and T45 were present in 68 brain tumours, including meningioma, astrocytoma, pituitary adenoma, neuroblastoma, metastasis to the brain, and cell lines.


RESULTS
CTNNB1 gene mutations were not found in either the original brain tumour specimens or the cell lines. However, a missense mutation of CTNNB1 was identified at residue 33, TCT (Ser) --> TGT (Cys) in a patient with lung metastasis to brain. In addition, in vitro functional assay showed that the S33C mutant of beta-catenin did affect transcriptional activity in a TCF-4-luciferase reporter construct.


CONCLUSIONS
These results indicate that the mutation of exon 3 of the CTNNB1 gene in brain tumours may be a rare event and yet may be required for a small subset of human metastatic brain tumours.
Lee
Chu-I
CI
Department of Medical Technology, Fooyin University, Kaohsiung, Taiwan, People's Republic of China.
Hsu
Meng-Yu
MY
Chou
Chia-Hua
CH
Wang
Chihuei
C
Lo
Yu-Shung
YS
Loh
Joon-Khim
JK
Howng
Shen-Long
SL
Hong
Yi-Ren
YR
D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000556:secondary; D002277:Carcinoma / Q000556:secondary; D020134:Catalytic Domain / Q000235:genetics; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000503:physiopathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D051176:beta Catenin / Q000235:genetics*
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D005819:Genetic Markers; D051153:Wnt Proteins; D051176:beta Catenin