Evaluation of the FHIT Gene in Colorectal Cancers

Thiagalingam, Sam; Lisitsyn, Nikolai A.; Hamaguchi, Masaaki; Wigler, Michael H.; Willson, James K. V.; Markowitz, Sanford D.; Leach, Frederick S.; Kinzler, Kenneth W.; Vogelstein, Bert

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Articles| July 01 1996

Evaluation of the FHIT Gene in Colorectal Cancers^¹

Sam Thiagalingam;

Sam Thiagalingam

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Nikolai A. Lisitsyn;

Nikolai A. Lisitsyn

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Masaaki Hamaguchi;

Masaaki Hamaguchi

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Michael H. Wigler;

Michael H. Wigler

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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James K. V. Willson;

James K. V. Willson

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Sanford D. Markowitz;

Sanford D. Markowitz

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Frederick S. Leach;

Frederick S. Leach

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Kenneth W. Kinzler;

Kenneth W. Kinzler

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Bert Vogelstein

The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [S. T., F. S. L., K. W. K., B. V.]

;

Department of Genetics, University of Pennsylvania

,

Philadelphia, Pennsylvania 9094 [N. A. L.]

;

Cold Spring Harbor Laboratory, Cold Spring Harbor

,

New York 11724 [M. H., M. H. W.]

;

Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University

,

Cleveland, Ohio 44106 [J. K. V. W., and S. D. M.]

; and

Howard Hughes Medical Institute [B. V.], The Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231

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Author & Article Information

²

To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231. Phone: (410) 955-8878; Fax: (410) 955-0548.

Received: April 30 1996

Accepted: May 15 1996

Online ISSN: 1538-7445

Print ISSN: 0008-5472

1996

Cancer Research, Inc.

Cancer Res (1996) 56 (13): 2936–2939.

Abstract

A variety of studies suggests that tumor suppressor loci on chromosome 3p are important in various forms of human neoplasia. Recently, a chromosome 3p14.2 gene called FHIT was discovered and proposed as a candidate tumor suppressor gene in colorectal and other cancers. We evaluated the FHIT gene in a panel of colorectal cancer cell lines and xenografts, which allowed a comprehensive mutational analysis. A transcript containing the complete coding sequence was found to be expressed at robust levels in 29 of 31 cancers tested. The complete sequence of the coding region of the gene was determined and found to be normal in all 29 of these cases. These studies suggest either that FHIT is inactivated by an unusual mechanism or that it plays a role in relatively few colorectal tumors.

¹

Supported by the Clayton Fund; NIH Grants CA35494, CA43460, CA09243, CA57208, CA57345, and CA62924; and American Cancer Society Grant FRA-451. B. V. is an Investigator of the Howard Hughes Medical Institute.

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1996

Cancer Research, Inc.

Evaluation of the FHIT Gene in Colorectal Cancers^¹

Abstract

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Evaluation of the FHIT Gene in Colorectal Cancers1

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Evaluation of the FHIT Gene in Colorectal Cancers^¹