Frameshift mutation of UVRAG , an autophagy-related gene, in gastric carcinomas with microsatellite instability

• Published in: Human pathology Vol. 39; no. 7; pp. 1059 - 1063
• Main Authors: Kim, Min Sung, BS, Jeong, Eun Goo, BS, Ahn, Chang Hyeok, MD, Kim, Sung Soo, MD, Lee, Sug Hyung, MD, Yoo, Nam Jin, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Elsevier; Elsevier Limited
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Aged; Apoptosis; Biological and medical sciences; Cancer; DNA Mutational Analysis; Female; Frameshift Mutation; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Humans; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Microdissection; Microsatellite Instability; Middle Aged; MSI; Mutation; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Single-Stranded Conformational; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Suppressor Proteins - genetics; Tumors; UVRAG; UVRAG; MSI; Mutation; Gastric cancer; Frameshift mutation; Malignant tumor; Autophagy; Stomach cancer; Stomach carcinoma; Anatomic pathology; Gene; Microsatellite DNA; Digestive diseases; Genetics; Instability; Cancer; Gastric disease
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2007.11.013

Summary Alteration of autophagy is involved in tumor development. Beclin1, an important regulator of autophagy, acts as a tumor suppressor. Ultraviolet (UV) radiation resistance–associated gene (UVRAG) binds with Beclin1 and induces autophagy. There is a polyadenine tract in UVRAG gene (A10 in exon 8) that is a target for frameshift mutations in colorectal carcinomas with microsatellite instability (MSI). Functionally, colon cancer cells with the frameshift mutation of UVRAG show reduced autophagy formation and increased tumorigenicity. The aim of this study was to determine whether the frameshift mutations of UVRAG are also present in gastric carcinomas with MSI. For this, we analyzed human UVRAG exon 8 in 45 gastric carcinomas with MSI and 92 gastric carcinomas without MSI by a single-strand conformation polymorphism analysis. Overall, we detected 3 frameshift mutations of UVRAG in the polyadenine tract (3/45; 6.7%), and all of them were found in MSH-high (H) subtypes (3/32; 9.4%). The 3 mutations consisted of 2 c.708_709delA and 1 c.709delA which would result in premature stops of the UVRAG protein synthesis. The present data indicate that frameshift mutations in the polyadenine tract in UVRAG gene are present in gastric carcinomas as well and suggest that the affected gastric cancer cells with the mutations may have a reduced autophagy activity.