Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability

Nam Gyun Kim, Hwanseok Rhee, Long Shan Li, Hyunki Kim, Jin Sung Lee, Joo Hang Kim, Kyu Kim Nam, Hoguen Kim

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5081-5087
Number of pages7
JournalOncogene
Volume21
Issue number33
DOIs
StatePublished - Aug 1 2002

Fingerprint

Microsatellite Instability
Colorectal Neoplasms
Genes
Frameshift Mutation
Mutation
Mutation Rate
Microsatellite Repeats
Neoplasms
Electrophoresis
N-methylsuccinimide
Carcinogenesis
Nucleotides
Gels
Databases
Polymerase Chain Reaction

Keywords

  • Coding mononucleotide repeats
  • Colorectal carcinoma
  • Dna mismatch repair
  • Frameshift mutation
  • Microsatellite instability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability. / Kim, Nam Gyun; Rhee, Hwanseok; Li, Long Shan; Kim, Hyunki; Lee, Jin Sung; Kim, Joo Hang; Nam, Kyu Kim; Kim, Hoguen.

In: Oncogene, Vol. 21, No. 33, 01.08.2002, p. 5081-5087.

Research output: Contribution to journalArticle

Kim, Nam Gyun ; Rhee, Hwanseok ; Li, Long Shan ; Kim, Hyunki ; Lee, Jin Sung ; Kim, Joo Hang ; Nam, Kyu Kim ; Kim, Hoguen. / Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability. In: Oncogene. 2002 ; Vol. 21, No. 33. pp. 5081-5087.
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abstract = "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.",
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AB - 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.

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