title: Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability.
abstract: Mounting evidence indicates that alterations of autophagy processes are directly involved in the development of many human diseases, including cancers. Autophagy-related gene (ATG) products are main players in the autophagy process. In humans there are 16 known ATG genes, of which four (ATG2B, ATG5, ATG9B and ATG12) have mononucleotide repeats with seven or more nucleotides. Frameshift mutations of genes with mononucleotide repeats are features of cancers with microsatellite instability (MSI). It is not known whether ATG genes with mononucleotide repeats are altered by frameshift mutations in gastric and colorectal carcinomas with MSI. For this, we analysed the mononecleotide repeats in ATG2B, ATG5, ATG9B and ATG12 in 32 gastric carcinomas with high MSI (MSI-H), 13 gastric carcinomas with low MSI (MSI-L), 43 colorectal carcinomas with MSI-H and 15 colorectal carcinomas with MSI-L by a single-strand conformation polymorphism (SSCP) analysis. We found ATG2B, ATG5, ATG9B and ATG12 mutations in 10, 2, 13 and 0 cancers, respectively. The mutations were detected in MSI-H cancers but not in MSI-L cancers. Gastric and colorectal cancers with MSI-H harboured one or more ATG mutations in 28.1% and 27.9%, respectively. Our data indicate that frameshift mutations in ATG genes with mononucleotide repeats are common in gastric and colorectal carcinomas with MSI-H, and suggest that these mutations may contribute to cancer development by deregulating the autophagy process.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Kang
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Yoo Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Chang Hyeok
authors.initials: CH
authors.lastname: Ahn
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001343:Autophagy / Q000235:genetics*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D053842:Microsatellite Instability; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009367:Neoplasm Staging; D018807:Polymorphism, Single-Stranded Conformational; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; C503283:ATG9B protein, human; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins