Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability.
Somatic frameshift mutations in some genes containing coding mononucleotide repeats (cMNRs) are well known characteristics of tumors with high microsatellite instability (MSI-H). We identified 22 novel and 11 known target genes containing cMNRs with a length of 10 or more nucleotides by using a systematic database search. Frameshift mutation analysis was performed with these 33 genes in 39 MSI-H and 24 microsatellite stable (MSS) colorectal carcinomas by assessing the mobility shifts of PCR products in gel electrophoresis and by sequencing. All the 39 MSI-H colorectal carcinomas, except one, showed mutations in more than one gene, while no mutations were found in 24 MSS colorectal carcinomas. Of these MSI-H tumors, 11 genes were mutated in more than 40%. The most frequently mutated novel genes were MARCKS (72%), FLJ11383 (74%) and TAF1B (82%). Biallelic inactivation in MARCKS and FLJ11383 was also frequent in MSI-H tumors. The observed mutation frequency of the 11 known target genes was compatible with that found by previous studies. The very high frequency of mutations, biallelic mutations and the predicted truncation of protein products suggests that mutations of MARCKS, FLJ11383 and TAF1B are selected, and play a role in the tumorigenesis of MSI-H colorectal carcinomas.
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Nam-Gyun
NG
Kim
Hwanseok
H
Rhee
Long Shan
LS
Li
Hyunki
H
Kim
Jin-Sung
JS
Lee
Joo-Hang
JH
Kim
Nam Kyu
NK
Kim
Hoguen
H
Kim
D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D030561:Databases, Nucleic Acid; D016368:Frameshift Mutation; D005959:Glucosidases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009363:Neoplasm Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020079:Terminal Repeat Sequences; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C463023:PCNX2 protein, human; D010750:Phosphoproteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D005959:Glucosidases; C070368:PRKCSH protein, human