Inactivation of both APC alleles in human and mouse tumors

Daniel B. Levy, Kelly J. Smith, Yasmin Beazer-Barclay, Stanley R. Hamilton, Bert Vogelstein, Kenneth W Kinzler

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5953-5958
Number of pages6
JournalCancer Research
Volume54
Issue number22
StatePublished - Nov 15 1994

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Adenomatous Polyposis Coli
Alleles
Neoplasms
APC Genes
Mutation
Germ-Line Mutation
Tumor Suppressor Genes
Adenoma
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Levy, D. B., Smith, K. J., Beazer-Barclay, Y., Hamilton, S. R., Vogelstein, B., & Kinzler, K. W. (1994). Inactivation of both APC alleles in human and mouse tumors. Cancer Research, 54(22), 5953-5958.

Inactivation of both APC alleles in human and mouse tumors. / Levy, Daniel B.; Smith, Kelly J.; Beazer-Barclay, Yasmin; Hamilton, Stanley R.; Vogelstein, Bert; Kinzler, Kenneth W.

In: Cancer Research, Vol. 54, No. 22, 15.11.1994, p. 5953-5958.

Research output: Contribution to journalArticle

Levy, DB, Smith, KJ, Beazer-Barclay, Y, Hamilton, SR, Vogelstein, B & Kinzler, KW 1994, 'Inactivation of both APC alleles in human and mouse tumors', Cancer Research, vol. 54, no. 22, pp. 5953-5958.
Levy DB, Smith KJ, Beazer-Barclay Y, Hamilton SR, Vogelstein B, Kinzler KW. Inactivation of both APC alleles in human and mouse tumors. Cancer Research. 1994 Nov 15;54(22):5953-5958.
Levy, Daniel B. ; Smith, Kelly J. ; Beazer-Barclay, Yasmin ; Hamilton, Stanley R. ; Vogelstein, Bert ; Kinzler, Kenneth W. / Inactivation of both APC alleles in human and mouse tumors. In: Cancer Research. 1994 ; Vol. 54, No. 22. pp. 5953-5958.
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