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.