Kj. Sohn et al., Molecular genetics of ulcerative colitis-associated colon cancer in the interleukin 2-and beta(2)-microglobulin-deficient mouse, CANCER RES, 61(18), 2001, pp. 6912-6917
Mice deficient in beta (2)-microglobulin and interleukin 2 (beta (2) M-null
X IL-2(null)) spontaneously develop colon cancer in the setting of chronic
ulcerative colitis (UC). We investigated mutations of the Ape and p53 gene
s and microsatellite instability in colonic adenocarcinomas arising in this
model. Mutations of the Ape and p53 genes in the regions corresponding to
mutation hot spots in human colorectal cancer were determined by sequencing
in 11 colonic adenocarcinomas. Microsatellite instability was determined i
n matched normal and neoplastic DNA at five loci. All 11 adenocarcinomas ha
rbored Ape mutations. Of these 11 tumors, 5 harbored truncating mutations.
A total of 67 Ape mutations were found in these 11 tumors; 59 were missense
mutations, whereas 8 were frameshift or nonsense mutations. Six of the 11
adenocarcinomas harbored p53 mutations. A total of seven p53 mutations were
found in these 11 tumors; all mutations were transitions, 4 of which were
C.G -->T:A transitions occurring in codon 229 at cytosine-guanine dinucleot
ides. Nine adenocarcinomas exhibited microsatellite instability in at least
one of the five loci examined; I tumor had microsatellite instability in t
wo loci. Molecular genetics, as well as clinical features, of colon cancer
in the beta (2)m(null) X IL-2(null) mice are similar to those of human UC-a
ssociated colorectal cancer. As such, this model appears to be an excellent
animal model to study UC-associated colorectal carcinogenesis.