Polymorphisms and probable lack of mutation in a human mutT homolog, hMTH1, in hereditary nonpoliposis colorectal cancer.

The human MTH1 gene, a homolog of the E. coli mutator gene mutT, encodes 8-oxo-dGTPase that degrades a mutagenic substrate for DNA synthesis. To determine whether this gene is associated with hereditary nonpolyposis colorectal cancer (HNPCC), we examined the hMTH1 sequence in 32 HNPCC cases by means of polymerase chain reaction-single strand conformation polymorphism and sequencing analyses. Three different DNA variants were identified in normal and the corresponding tumor DNA. The first variant, a G to A transition at codon 83, changes valine to methionine and was detected in 9 HNPCC cases. The same change was detected in 5 of 30 unrelated healthy individuals, suggesting that it is not associated with a marked HNPCC predisposition. The second variant is a silent C to T transition at codon 119. Another C to T transition at 31 bp upstream of the beginning of exon 4 was also found. However, specific mutations in hMTH1 were detected in neither normal nor tumor cells from HNPCC patients. These results indicate that hMTH1 is not directly involved in HNPCC.