Microsatellite Instability and Frameshift Mutations in the Bax Gene in Hereditary Nonpolyposis Colorectal Carcinoma

• Published in: Cancer science Vol. 89; no. 10; pp. 1020 - 1027
• Main Authors: Sakao, Yukinori, Noro, Masahiro, Sekine, Shigeki, Nozue, Mutsumi, Hirohashi, Setsuo, Itoh, Tsuyoshi, Noguchi, Masayuki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.1998; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: BAX gene; bcl-2-Associated X Protein; Biological and medical sciences; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology; Colorectal Neoplasms, Hereditary Nonpolyposis - surgery; Conformation; Dinucleotide Repeats; DNA repair; Frameshift Mutation; Gastroenterology. Liver. Pancreas. Abdomen; Gene polymorphism; Genes; Genetic Markers; Hereditary nonpolyposis colorectal cancer; Humans; Medical sciences; Microsatellite instability; Microsatellite Repeats; Mismatch repair; Mutation; Phenotype; Phenotypes; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes; Risk Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumorigenesis; Tumors; Human; Immunohistochemistry; Rectal disease; Carcinoma; Malignant tumor; Carcinogenesis; Single strand conformation polymorphism; Colonic disease; Polymerase chain reaction; Pathology; Microsatellite DNA; C-Onc gene; Rectum; Digestive diseases; Intestinal disease; Familial cancer; Instability; Colon; Mutation; Molecular biology; Protooncogene
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1998.tb00491.x

We studied microsatellite instability (MI) and bax gene abnormalities in colorectal carcinomas from 36 patients diagnosed as having hereditary nonpolyposis colorectal cancers (HNPCC) according to the clinical criteria (12 with confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and from 20 randomly selected patients with other colorectal cancers. MI was examined at 4 dinucleotide microsatellite loci and one mononucleotide locus. Frameshift mutations in the bax gene were detected by polymerase chain reaction‐single strand conformation polymorphism analysis. MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B. Three MI patterns were identified: type 1, MI in both mono‐ and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide repeats. Most MI‐positive patients in group A showed type 1 MI, whereas in group B, 5 showed type 1, 3 showed type 2 and 4 showed type 3. Frameshift mutations in the bax gene correlated strongly with type 1 and type 2 MI. These results indicate that mutations of different DNA mismatch repair genes may cause several types of MI and result in several different clinical phenotypes of HNPCC. The bax gene may be one of the target genes which play a role in the tumorigenesis of HNPCC.