Frameshift Mutations of HSPA4 and MED13 in Gastric and Colorectal Cancers.

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.

Frameshift mutations in mammalian target of rapamycin pathway genes and their regional heterogeneity in sporadic colorectal cancers.

Mammalian target of rapamycin (mTOR) pathway is known to be involved in cancer pathogenesis. The aim of our study was to find whether mTOR-related genes were mutated and expressionally altered in colorectal cancers (CRCs). Through public database searching, we found that PIK3CB, insulin receptor substrate 1/2 (IRS1), RPS6, EIF4B, RPS6KA5, and PRKAA2 that were known as mTOR-related genes possessed mononucleotide repeats in DNA coding sequences that could be mutated in cancers with microsatellite instability (MSI).

Regional Bias of Intratumoral Genetic Heterogeneity of Apoptosis-Related Genes BAX, APAF1, and FLASH in Colon Cancers with High Microsatellite Instability.

Background: Apoptosis inactivation and intratumoral heterogeneity (ITH) are common features of cancers, including colorectal cancer (CRC). Inactivation of apoptosis prolongs cancer cell survival, and ITH may contribute to CRC progression.

Aim: To examine the presence and extent of mutational ITH in the pro-apoptotic genes APAF1, BAX, and FLASH and the association of mutational ITH with pathologic parameters of CRC.

Laminin gene LAMB4 is somatically mutated and expressionally altered in gastric and colorectal cancers.

Laminins are important in tumor invasion and metastasis as well as in maintenance of normal epithelial cell structures. However, mutation status of laminin chain-encoding genes remains unknown in cancers. Aim of this study was to explore whether laminin chain genes are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC).

Frameshift mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in gastric and colorectal cancers with high microsatellite instability.

Histone methyltransferase (HMT), which catalyzes a histone methylation, is frequently altered in cancers at mutation and expression levels. The aims of this study were to explore whether SETD1B, SETDB2, and SETD2, SET domain-containing HMT genes, are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). In a public database, we found that SETD1B, SETDB2, and SETD2 had mononucleotide repeats in coding sequences that might be mutation targets in cancers with microsatellite instability (MSI).

Mutational and expressional analysis of ERBB3 gene in common solid cancers.

ERBB3 is a member of EGFR family receptor tyrosine kinases, genetic alterations of which are common and therapeutically targeted in human cancers. Recently, somatic mutations of ERBB3 gene, including recurrent mutation in exon 3 altering Val104, were reported in gastric cancers (GC) and colorectal cancers (CRC), strongly suggesting its role in the development of GC and CRC. To examine whether the recurrent ERBB3 mutations of exon 3 occur in GC and CRC, and other malignancies as well, we analyzed the ERBB3 in 1677 cancer tissues by a single-strand conformation polymorphism (SSCP) assay.

Frameshift mutations of axon guidance genes ROBO1 and ROBO2 in gastric and colorectal cancers with microsatellite instability.

Aims: Several lines of evidence indicate that axon guidance genes are involved not only in neural development but also in cancer development. ROBO1 and ROBO2, crucial regulators of axon guidance, are considered potential tumour suppressor genes. The aim of this study was to explore whether ROBO1 and ROBO2 genes are somatically mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC).