Mutation analysis of Smad4 gene in sporadic colorectal cancer
Date Issued
2007
Date
2007
Author(s)
Taso, Hsiao-Mei
DOI
en-US
Abstract
Colorectal cancer is currently the third most common cancer in Taiwan. Over the past decade, the mortality rate of colorectal cancer has increased remarkably. Therefore, it has become an important public health issue these days. The initiation and progression of colorectal cancer is a multi-step process leading to the accumulation of genomic alterations occurring over the lifetime of a tumor. Chromosome 18q21 is one of the most frequently lost regions in colorectal cancer. There are three candidate tumor suppressor genes located in this region, including DCC, Smad2 and Smad4. Since accumulated evidence has failed to support DCC and Smad2 as tumor suppressor genes involved in colorectal carcinogenesis, Smad4 seems to be the major one. However, there is a gap existing between chromosome loss of 18q and mutations of Smad4.
In our study, we reconfirmed the status of 18q and screened all the coding region of Smad4 gene for small mutations. Furthermore, we performed a novel method, multiplex ligation-dependent probe amplification (MLPA), to detect copy number changes of Smad4. Among 63 patients analyzed, 19 (30.2%) mutations were identified and only two were found by conventional mutation detection methods. By using MLPA, the frequency of Smad4 mutations was raised. Although the relative low frequency of Smad4 inactivation (30.2%) contrasts with the high frequency of LoH at 18q21 (42.4%), it may implicate that Smad4 is the major tumor suppressor gene contributing to colorectal carcinogenesis in 18q21 region.
Subjects
大腸直腸癌
第十八條染色體缺失
Smad4基因
MLPA技術
Colorectal cancer
Chromosome 18q loss
Smad4
MLPA
SDGs
Type
other
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