title: Clinicopathologic characteristics related to the high variability of coding mononucleotide repeat sequences in tumors with high-microsatellite instability.
abstract: Frameshift mutation at coding mononucleotide repeat sequences are common in tumors with microsatellite instability (MSI-H), but the incidences are different among the target genes. We analyzed the mutational profiles of 12 known target genes containing polydeoxyadenosine repeats in their coding sequences in 39 MSI-H colorectal carcinomas and 40 MSI-H gastric carcinomas by using polymerase chain reaction and sequencing, and compared the results with the clinicopathologic characteristics. Frameshift mutations of target genes in the MSI-H colorectal and gastric carcinomas are increased according to the length of the polydeoxyadenosine repeats in the target genes. The mean mutational rates of MSI-H colorectal carcinomas and MSI-H gastric carcinomas were 2.03 and 1.95 in the 4 genes containing (A)10 repeats, 1.23 and 0.73 in the 4 genes with (A)9 repeats and 0.61 and 0.48 in the 4 genes containing (A)8 repeats, respectively (p<0.001). Among the evaluated clinicopathologic findings, intestinal type gastric carcinomas had more frameshift mutations than the diffuse type carcinomas (3.5 vs. 1.9, p=0.01). These findings suggest that mutational rates of the target genes in MSI-H tumors are diverse, and higher mutational rates are related to the length of mononucleotide repeat sequences of the target genes and histologic type of tumors.
authors.affiliation: Department of Thoracic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Chung
authors.forename: Nam-Gyun
authors.initials: NG
authors.lastname: Kim
authors.forename: Long Shan
authors.initials: LS
authors.lastname: Li
authors.forename: Haeryoung
authors.initials: H
authors.lastname: Kim
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.forename: Chung Mo
authors.initials: CM
authors.lastname: Nam
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005787:Gene Frequency; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D009077:Mucins; D009363:Neoplasm Proteins