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Advances in Brief

Close Correlation between Mutations of E2F4 and hMSH3 Genes in Colorectal Cancers with Microsatellite Instability

Masahiko Ikeda, Hideo Orimo, Hiroki Moriyama, Eiitsu Nakajima, Nagahide Matsubara, Ryuichi Mibu, Noriaki Tanaka, Takashi Shimada, Akinori Kimura and Kenji Shimizu
Masahiko Ikeda
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Hideo Orimo
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Hiroki Moriyama
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Eiitsu Nakajima
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Nagahide Matsubara
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Ryuichi Mibu
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Noriaki Tanaka
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Takashi Shimada
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Akinori Kimura
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Kenji Shimizu
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DOI:  Published February 1998
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Abstract

Defects in mismatch repair function can lead to the microsatellite instability (MI+; replication error) phenotype in certain human cancers. We previously reported that MI+ tumor-specific repeat number alteration at 13 consecutive trinucleotide (CAG) repeats within a coding exon of the E2F4 gene is a possible target of the defective repair pathway. Additional investigations revealed that E2F4 mutations are common (11 of 17 cases, 65%, mostly deletions) in a subset of human colorectal cancers with extensive MI+ phenotype, with respect to the proportion of loci affected and that most of these E2F4-mutated tumors (9 of 11, 82%) were accompanied by frameshift mutations in a polyadenine stretch within the seventh exon of the hMSH3 gene, a known mismatch repair gene that is responsible for repair of mismatch loops of two to four nucleotides. However, neither of these mutations was detected in 15 tumors with a lower incidence of MI+ loci. Similar repeat number alterations were less frequent in CAG repeats from other genes in all of the MI+ tumors we examined. These results indicate the presence of a novel cascade of mutational events that may be involved in acquisition of the malignant phenotype of human colorectal cancers with genetic instability.

Footnotes

  • ↵1 Supported by Grants-in-Aid 07671306, 08671368 (to N. M.) 07272103, and 08457049 from the Ministry of Education, Science, Sports and Culture and by grants-in-aid from the Ministry of Health and Welfare of Japan (to K. S.).

  • ↵2 To whom requests for reprints should be addressed, at Department of Molecular Genetics, Institute of Cellular and Molecular Biology, Okayama University Medical School, Shikata-cho 2-5-1, Okayama 700-8558, Japan. Phone: 81-86-235-7378; Fax: 81-86-235-7383; E-mail: shimke47@med.okayama-u.ac.jp.

  • Received October 16, 1997.
  • Accepted January 2, 1998.
  • ©1998 American Association for Cancer Research.
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February 1998
Volume 58, Issue 4
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Close Correlation between Mutations of E2F4 and hMSH3 Genes in Colorectal Cancers with Microsatellite Instability
Masahiko Ikeda, Hideo Orimo, Hiroki Moriyama, Eiitsu Nakajima, Nagahide Matsubara, Ryuichi Mibu, Noriaki Tanaka, Takashi Shimada, Akinori Kimura and Kenji Shimizu
Cancer Res February 15 1998 (58) (4) 594-598;

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Close Correlation between Mutations of E2F4 and hMSH3 Genes in Colorectal Cancers with Microsatellite Instability
Masahiko Ikeda, Hideo Orimo, Hiroki Moriyama, Eiitsu Nakajima, Nagahide Matsubara, Ryuichi Mibu, Noriaki Tanaka, Takashi Shimada, Akinori Kimura and Kenji Shimizu
Cancer Res February 15 1998 (58) (4) 594-598;
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