title: Frameshift Mutations of HSPA4 and MED13 in Gastric and Colorectal Cancers.
abstract: Frameshift mutation of genes containing mononucleotide repeats is a feature of gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). In the public genome database, we found that human HSPA4 gene encoding a heats hock protein 70 protein (HSP70-4) and MED13 gene had mononucleotide repeats in the coding sequences that could be targets for frameshift mutation in cancers with MSI. HSP70-4 is a member of HSP70 that is known to play a role in cell survival. MED13 is a member of MED genome-wide transcription regulators that function as a regulator for diverse biological processes. In this study, we analyzed the mutations in 79 GCs and 124 CRCs including high MSI (MSI-H) and microsatellite stable/low MSI (MSS/MSI-L) cases by single-strand conformation polymorphism analysis and DNA sequencing. We found frameshift mutations of HSPA4 gene in two cancers (one GC and one CRC) and MED13 gene in the other two cancers (one GC and one CRC). The frameshift mutations were deletions of one base (c.2396delA (p.Asn799MetfsX50)) in HSPA4 and (c.2175delA (p.Lys725AsnfsX4)) in MED13. Each of HSPA4 and MED13 mutations were detected in GC with MSI-H (1/34: 2.9 %) and CRC with MSI-H (1/79: 1.3 %), but not in those with MSS. Our data show that unconventional HSPA4 and MED13 genes harbored frameshift mutations in GC and CRC with MSI. These mutations might possibly inactivate their functions and could be a feature of GC and CRC with MSI-H.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Yun Sol
authors.initials: YS
authors.lastname: Jo
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Mi Ryoung
authors.initials: MR
authors.lastname: Choi
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea. suhulee@catholic.ac.kr.
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D053842:Microsatellite Instability; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D050957:HSP110 Heat-Shock Proteins; C121993:HSPA4 protein, human; C488666:MED13 protein, human; D056892:Mediator Complex
keywords: Cancers; HSP70; HSPA4; MED13; Microsatellite instability; Mutation