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Inactivation of Both APC Alleles in Human and Mouse Tumors

Daniel B. Levy, Kelly J. Smith, Yasmin Beazer-Barclay, Stanley R. Hamilton, Bert Vogelstein and Kenneth W. Kinzler
Daniel B. Levy
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Kelly J. Smith
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Yasmin Beazer-Barclay
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Stanley R. Hamilton
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Bert Vogelstein
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Kenneth W. Kinzler
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DOI:  Published November 1994
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Abstract

Germline mutations of the adenomatous polyposis coli (APC) gene lead to multiple intestinal tumors in familial adenomatous polyposis patients and in multiple intestinal neoplasia (Min) mice. Current models predict that inactivation of the remaining normal allele of a tumor suppressor gene is rate limiting for tumor formation, but this has been difficult to prove. While examination of colorectal adenomas from familial adenomatous polyposis patients identified somatic inactivating mutations of the second allele in the majority of tumors (19 of 24), the absolute requirement for an early inactivating event could not be demonstrated. In contrast, inactivation of the remaining allele of the murine APC (Apc) could be demonstrated in 100% (30 of 30) of tumors from Min mice. Moreover, inactivation was observed in the earliest recognizable phase of tumors, including some lesions containing as few as two dysplastic crypts. These results suggest that the mutation of the second APC allele is an early event in Min and familial adenomatous polyposis tumorigenesis, supporting Knudson's hypothesis.

Footnotes

  • ↵1 This work was supported by NIH Grants GM-07184, CA-62924, and CA-57345. B. V. is an American Cancer Society Research Professor.

  • ↵2 To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, 424 N. Bond St., Room 109, Baltimore, MD 21231.

  • Received May 4, 1994.
  • Accepted September 19, 1994.
  • ©1994 American Association for Cancer Research.
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November 1994
Volume 54, Issue 22
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Inactivation of Both APC Alleles in Human and Mouse Tumors
Daniel B. Levy, Kelly J. Smith, Yasmin Beazer-Barclay, Stanley R. Hamilton, Bert Vogelstein and Kenneth W. Kinzler
Cancer Res November 15 1994 (54) (22) 5953-5958;

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Inactivation of Both APC Alleles in Human and Mouse Tumors
Daniel B. Levy, Kelly J. Smith, Yasmin Beazer-Barclay, Stanley R. Hamilton, Bert Vogelstein and Kenneth W. Kinzler
Cancer Res November 15 1994 (54) (22) 5953-5958;
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