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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-8-12
pubmed:abstractText
beta-catenin mutations have been identified in a variety of human malignancies; most of these are missense mutations restricted at hot-spot areas in exon 3. beta-catenin mutations are known to be highly associated with colorectal cancers with microsatellite instability (MSI). More than 70 beta-catenin mutations have been reported in colorectal cancers, and approximately 90% of beta-catenin mutations have been found in 11 codons (codons 29, 31, 32, 33, 34, 35, 37, 38, 41, 45, and 48) as missense mutations or in-frame deletions. We have developed an oligonucleotide microarray for detecting beta-catenin mutations at these 11 codons. The developed oligonucleotide microarray can detect a total of 110 types of beta-catenin mutations, including the 60 mutations reported previously. Nine beta-catenin mutations were identified in this study by five different methods, i.e., PCR- single-strand conformational polymorphism, denaturing high performance liquid chromatography, direct sequencing, cloning-sequencing, and with an oligonucleotide microarray. All nine of the mutations were identified by denaturing high performance liquid chromatography, cloning-sequencing, and by the oligonucleotide microarray. However, PCR-single-strand conformational polymorphism missed 1 beta-catenin mutation and direct sequencing missed 2. Five beta-catenin mutations from 74 colorectal carcinomas (34 proximal colon cancers and 40 distal colorectal cancers) and 4 beta-catenin mutations from 31 colorectal cancer cell lines (7 from the proximal colon, 6 from the distal colorectum, and 18 unknown) were identified. In colorectal carcinomas, all 5 of the beta-catenin mutations were found in proximal colon tumors. In colorectal cancer cell lines, 2 of 4 cell lines with beta-catenin mutations originated from the proximal colon, and the remaining 2 cell lines were simply described as having originated from the colon. Considering the relationships among beta-catenin mutations, MSI, and tumor location, the frequency of beta-catenin mutations was found to be meaningfully higher in colorectal carcinomas with MSI than in those with microsatellite stability (P < 0.001); moreover, MSI was found to be more frequent in proximal colon tumors (P < 0.01). In addition, beta-catenin mutations were also found to be associated with proximal colon cancer (P = 0.017).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2920-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12912937-Adult, pubmed-meshheading:12912937-Cell Line, Tumor, pubmed-meshheading:12912937-Chromatography, High Pressure Liquid, pubmed-meshheading:12912937-Cloning, Molecular, pubmed-meshheading:12912937-Colonic Neoplasms, pubmed-meshheading:12912937-Cytoskeletal Proteins, pubmed-meshheading:12912937-DNA Mutational Analysis, pubmed-meshheading:12912937-DNA Sequence, Unstable, pubmed-meshheading:12912937-Gene Deletion, pubmed-meshheading:12912937-Humans, pubmed-meshheading:12912937-Male, pubmed-meshheading:12912937-Microsatellite Repeats, pubmed-meshheading:12912937-Middle Aged, pubmed-meshheading:12912937-Mutation, pubmed-meshheading:12912937-Mutation, Missense, pubmed-meshheading:12912937-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:12912937-Polymerase Chain Reaction, pubmed-meshheading:12912937-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:12912937-Trans-Activators, pubmed-meshheading:12912937-beta Catenin
pubmed:year
2003
pubmed:articleTitle
Development and applications of a beta-catenin oligonucleotide microarray: beta-catenin mutations are dominantly found in the proximal colon cancers with microsatellite instability.
pubmed:affiliation
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi 411-764, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't