Somatic mutational mechanisms involved in intestinal tumor formation in Min mice
Shoemaker, A.R.; Luongo, C.; Moser, A.R.; Marton, L.J.; Dove, W.F.
Cancer Research 57(10): 1999-2006
1997
ISSN/ISBN: 0008-5472 PMID: 9157997 Document Number: 470500
We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc) allele and that intestinal tumor multiplicity in B6 Min/+ mice can be significantly increased by treatment with a single dose of N-ethyl-N-nitrosourea (ENU). Here, we show that some tumors from ENU-treated Min/+ mice can form without complete elimination of Apc+. At least 25% of these tumors acquired somatic Apc truncation mutations. Interestingly, some ENU-induced tumors demonstrated loss of the Apc+ allelic marker examined by the quantitative PCR assay used here. Using two methods of mutation detection, we identified no Apc mutations in at least 12% of the tumors from ENU-treated B6 Min/+ mice. Finally, no H- or K-ras-activating mutations were detected in intestinal tumors from either untreated or ENU-treated Min/+ mice. The majority of somatic human APC mutations in intestinal tumors lead to APC truncation. Our results demonstrate that somatic Apc truncation mutations also frequently occur in ENU-induced intestinal tumors in Min mice.