Alterations of the base excision repair gene MUTYH in sporadic colorectal             cancer.
The base excision repair gene MUTYH encodes glycosylase which removes adenine             residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic             germline mutations of the MUTYH gene are known to cause multiple colorectal adenomas             including polyposis and cancer, mostly due to G:C➝T:A transversions in proto-oncogenes             or tumor suppressor genes. The risk of colorectal cancer (CRC) in monoallelic             mutation carriers of MUTYH is estimated to be higher in comparison with non-carriers.             To investigate the possible role in sporadic CRC, we examined alterations of the             MUTYH gene including somatic mutations and allelic loss in 101 cases of sporadic             CRC, together with the KRAS mutation in some cases. MUTYH mutations in cancer             DNA were detected in 3 cases, while mutations were also found in DNA samples from             normal tissues, indicating that all were germline mutations. Allelic loss at the             MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS mutations were found             in 33 of the 101 (32.7%) samples. There was no significant difference in the rate             of G:C➝T:A transversion in KRAS between cases with allelic loss (1 of 10, 10.0%)             and without allelic loss (9 of 41, 22.0%). Investigation of quantitative allelic             imbalance at SNP rs3219489 of MUTYH showed that CRC cases with C allele dominance             (minor type corresponding to His) were more frequently detected with G:C➝T:A transversions             than in those with G allele dominance (major type corresponding to Gln). In conclusion,             somatic alterations of MUTYH in sporadic CRC were rare, similar to other DNA repair             genes. However, it is possible that unknown mutations of regions not analyzed             in this study and epigenetic changes of the promoter region of MUTYH may contribute             to the disease.
Division of Lower Gastroenterology, Department of Surgery, Hyogo                     College of Medicine, Nishinomiya, Japan.
Takashi
T
Kuno
Nagahide
N
Matsubara
Satoshi
S
Tsuda
Masayoshi
M
Kobayashi
Mie
M
Hamanaka
Daisuke
D
Yamagishi
Kiyoshi
K
Tsukamoto
Tomoki
T
Yamano
Masafumi
M
Noda
Hiroki
H
Ikeuchi
Sanghyuk
S
Kim
Kazuo
K
Tamura
Naohiro
N
Tomita
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase