Reference SummaryLevy DB, Cancer Res 1994 Nov 15;54(22):5953-8

Title

Inactivation of both APC alleles in human and mouse tumors.

Authors

Levy DB; Smith KJ; Beazer-Barclay Y; Hamilton SR; Vogelstein B; Kinzler KW

Journal

Cancer Res

Volume

54

Issue

22

Year

1994

Pages

5953-8

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.

Links

J:21856 – Mouse Genome Informatics
7954428 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Jejunum adenoma Intestine - Small Intestine - Jejunum

observed

C57BL/6J-ApcMin/+ Intestine adenoma Intestine

observed

C57BL/6J-ApcMin/+ Intestine dysplasia Intestine

observed