Development and Applications of a (cid:1) -Catenin Oligonucleotide Microarray: (cid:1) -Catenin Mutations Are Dominantly Found in the Proximal Colon Cancers with Microsatellite Instability 1

(cid:1) -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. (cid:1) -catenin mutations are known to be highly associated with colorectal cancers with microsatellite instability (MSI). More than 70 (cid:1) -catenin mutations have been reported in colorectal cancers, and (cid:1) 90% of (cid:1) -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 (cid:1) -catenin mutations at these 11 codons. The developed oligonucleotide microarray can detect a total of 110 types of (cid:1) -catenin mutations, including the 60 mutations reported previously. Nine (cid:1) -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 (cid:1) -catenin mutation and direct sequencing missed 2. Five (cid:1) -catenin mutations from 74 colorectal carcinomas (34 proximal colon cancers and 40 distal colorectal cancers) and 4 (cid:1) -catenin mutations from 31 colorectal cancer cell lines (7 from the proximal colon, 6 from the distal colorectum, and 18 unknown) were

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