Instabilotyping : Comprehensive identification of frameshift mutations caused by coding region microsatellite instability

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 16; pp. 6046 - 6049
• Main Authors: MORI, Yuriko, JING YIN, RASHID, Asma, LEGGETT, Barbara A, YOUNG, Joanne, SIMMS, Lisa, KUEHL, Peter M, LANGENBERG, Patricia, MELTZER, Stephen J, STINE, O. Colin
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2001
• Subjects: 3' Untranslated Regions - genetics; activin receptors; Activin Receptors, Type II; bcl-2-Associated X Protein; Biological and medical sciences; Colorectal Neoplasms - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Electron Transport Complex I; Frameshift Mutation - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Medical sciences; Microsatellite Repeats - genetics; Multidrug Resistance-Associated Proteins; MutS Homolog 3 Protein; NADH, NADPH Oxidoreductases - genetics; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Receptors, Growth Factor - genetics; Receptors, Transforming Growth Factor beta - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; TGFBR2 gene; Tumors; Human; Rectal disease; Nucleotide sequence; Pathogenesis; Tumoral tissue; Frameshift mutation; Malignant tumor; Carcinogenesis; In vitro; Colonic disease; Gene; Microsatellite DNA; Rectum; Digestive diseases; Intestinal disease; Instability; Colon; Locus
• ISSN: 0008-5472; 1538-7445

Coding region frameshift mutation caused by microsatellite instability (MSI) is one mechanism contributing to tumorigenesis in cancers with MSI in high frequency. Mutation of TGFBR2 is one example of this process. To identify additional examples, a large-scale genomic screen of coding region microsatellites was conducted. 1115 coding homopolymeric loci with six or more nucleotides were identified in an online genetic database. Mutational screening was performed at 152 of these loci in 46 colorectal tumors with MSI in high frequency. Nine loci were mutated in > or =20% of tumors, 10 loci in 10-20%, 24 loci in 5-10%, 43 loci in <5%, and 66 loci were not mutated in any tumors. The most frequently mutated novel loci were the activin type II receptor gene (58.1%), SEC63 (48.8%), AIM 2 (47.6%), a gene encoding a subunit of the NADH-ubiquinone oxidoreductase complex (27.9%), a homologue of mouse cordon-bleu (23.8%), and EBP1/PA2G4 (20.9%). This genome-wide approach identifies coding region MSI in genes or pathways not implicated previously in colorectal tumorigenesis, which may merit functional study or other additional analysis.