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| 篇名 |
Primary Mutation of Exon 3 β of -catenin (CTNNB1)Gene in Colorectal Tumors: Correlation with Mutation ofAdenomatous Polyposis Coli Gene, Microsatellite Instability,and Prognostic Significance |
| 作者 |
Jin-Tung Liang, Kuo-Chin Huang*, Hong-Shiee Lai, Po-Huang Lee |
| 卷期/出版年月 |
39卷6期 (2006/12) |
| 頁次 |
279-292 |
| 摘要 |
We explore the mutational patterns of the exon 3 of the β-catenin
(CTNNB1) gene in colorectal tumors and assess whether primary mutation in this
region is associated with mutation of the adenomatous polyposis coli (APC) gene, highfrequency
microsatellite instability (MSI-H), and prognostic significance.
Methods: The mutational patterns of the exon 3 of the β -catenin gene in 464
colorectal tumors were assessed by direct DNA sequencing of polymerase chain
reaction-amplified products. Mutation of APC gene was first analyzed by topographic
Denaturing High Performance Liquid Chromatography, followed by direct DNA
sequencing and protein truncation test. The subcellular localization of βof MSI in at
least 2 of the 5 examined chromosomal loci (BAT-25, BAT-26, D5S346, D2S123,
D17S250).
Results: We found that primary mutation of the βatenin gene in colorectal tumors
was very low (n=12, 2.59%) in incidence. Besides previously reported conserved
mutational sites including codon 34,37,41 and 45, two novel mutations in codon 59
(threonine alanine) and 60 (serine alanine)were detected. The colorectal tumors
with mutation in codon 59 or 60 seem to be similar to those with mutation in codon 34,
37, 41, or 45 in terms of nuclear translocation of β-catenin, mutational status of the
APC gene, and other clinicopathologic features. Compared to the control group (n=48),
randomly selected from the 452 tumors with wild-type β-catenin, tumors with
primary β-catenin mutation tended to present with nuclear accumulation of β-
catenin protein (p=0.015). Primary β-catenin mutation was mutually exclusive with
the mutation of APC gene in advanced colorectal cancer (p 0.001). Moreover, the
mutational rate of β-catenin was significantly higher in tumors with MSI-H (p<0.001).
Multivariate analysis indicated that MSI-H was a significantly (p=0.045) independent
favorable prognostic factor with a relative risk of 0.112 (95% Confidence Interval:
0.013-0.954). However, primary mutation in exon 3 of the β-catenin gene, nuclear -β
catenin expression, and APC mutation were without prognostic significance.
Conclusions: DNA sequences encoding the regulatory domain of β-catenin protein
may extend from codon 29 to codon 60 in the exon 3 of this gene. Primary mutation of
exon 3 of the β-catenin gene was very rare in colorectal tumors, mutually exclusive
with APC mutation only in advanced disease, and associated with MSI-H. |
| 關鍵詞 |
β-catenin, CTNNB1, APC gene, microsatellite instability, colorectal cancer |
| 分類 |
Original Article |
|
