To determine the relationship between the mutation of the PTEN gene and gen
omic instability in human colorectal. cancer, we screened the PTEN gene in
32 colorectal cancers (eight cell lines and 24 tissues) displaying microsat
ellite instability (MSI) and 32 colorectal cancers (six cell lines and 26 t
issues) displaying microsatellite stability (MSS). Of 64 samples, six frame
shift mutations were identified in six MSI colorectal cancers (two cell lin
es and four tumor tissues) but not in MSS colorectal cancers. Of the six MS
I colorectal cancers containing PTEN mutation, two case (one cell line and
one tumor tissue) showed biallelic mutation of PTEN. Furthermore, to compar
e the frequency of PTEN mutation with that of other MSI target genes, the m
ononucleotide repeat sequences of TGF-beta RII, BAX, IGFIIR, hMSH6 and hMSH
3 were analyzed. The frequencies of frameshift mutation were revealed 78% i
n TGF-beta RII, 56% in BAX, 46.9% in hMSH3, 37.5% in hMSH6,21.9% in IGFIIR,
and 18.8% in PTEN. These results suggest that the PTEN gene is a target of
genomic instability in MSI colorectal tumorigenesis. (C) 2001 Elsevier Sci
ence Ireland Ltd. All rights reserved.