Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas.
BACKGROUND
Most investigations on MutY human homolog (MYH)-associated polyposis (MAP) have been conducted in Western countries. Limited data on MAP in Asia are currently available. The present study investigated germline mutations of the MYH gene among patients with 10 to 99 adenomatous colorectal polyps and familial adenomatous polyposis (FAP) without adenomatous polyposis coli (APC) germline mutations in Korea.


METHODS
The study population included 46 patients with 10 to 99 adenomatous polyps in the colorectum and 16 FAP patients with no identified APC germline mutations. Subjects were screened for MYH germline mutations, and we additionally screened for MYH mutations in 96 normal control individuals.


RESULTS
Two of 46 (4.3%) patients with multiple polyps displayed heterozygous biallelic germline mutations of the MYH gene. A 39-year-old male patient with biallelic MYH mutations (p.G272E and p.A359V) received total proctocolectomy for rectal cancer and 36 colorectal polyps. A 58-year-old female patient with biallelic MYH mutations (p.Q253X and p.Q440P) received right hemicolectomy for ascending colon cancer and 16 colonic polyps. The frequency of biallelic MYH mutation in 14 of 46 multiple-polyp patients, who had 15 to 99 polyps, was 14.3% (2 of 14). No biallelic MYH mutations were detected in the 32 patients with 10 to 14 colorectal polyps, 16 FAP patients, or 96 normal controls.


CONCLUSIONS
We identified biallelic MYH germline mutations in 2 of 14 (14.3%) Korean patients with 15 to 99 colorectal polyps. In this study, there was no Y165C or G382D hot-spot mutation, which had been reported most frequently in previous studies.
Kim
Duck-Woo
DW
Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Chongno-Gu, Seoul, South Korea.
Kim
Il-Jin
IJ
Kang
Hio-Chung
HC
Jang
Sang-Geun
SG
Kim
Kun
K
Yoon
Hyun-Ju
HJ
Ahn
Sun-A
SA
Han
Song Yee
SY
Hong
Seung-Hyun
SH
Hwang
Jung-A
JA
Sohn
Dae Kyung
DK
Jeong
Seung-Yong
SY
Choi
Hyo Seong
HS
Hong
Chang Won
CW
Lim
Seok-Byung
SB
Park
Jae-Gahb
JG
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001483:Base Sequence; D003111:Colonic Polyps / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
Am J Hum Genet. 2005 Jul;77(1):112-9
15931596
J Bacteriol. 1992 Oct;174(20):6321-5
1328155
Cancer Res. 2003 Nov 15;63(22):7595-9
14633673
Nat Genet. 2002 Feb;30(2):227-32
11818965
Gastroenterology. 2004 Jul;127(1):9-16
15236166
Lancet. 2003 Jul 5;362(9377):39-41
12853198
J Natl Cancer Inst. 2004 Nov 3;96(21):1631-4
15523092
Hum Mutat. 2005 Sep;26(3):281
16088911
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-20
9223306
Mutat Res. 2005 Oct 15;578(1-2):430-3
15890374
Int J Cancer. 2006 Aug 15;119(4):807-14
16557584
Nature. 1991 Jan 31;349(6308):431-4
1992344
J Med Genet. 2005 Sep;42(9):e54
16140997
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):312-4
16492921
Dis Colon Rectum. 2006 Feb;49(2):272-5
16416081
Hum Mol Genet. 2002 Nov 1;11(23):2961-7
12393807
Carcinogenesis. 2004 Oct;25(10):1859-66
15180946
J Hum Genet. 1999;44(2):103-8
10083733
Gastroenterology. 2004 Jun;126(7):1681-5
15188161
J Biol Chem. 1993 Nov 5;268(31):23524-30
8226881
Br J Cancer. 2006 Jul 17;95(2):239-42
16804517
J Bacteriol. 1996 Jul;178(13):3885-92
8682794
N Engl J Med. 2003 Feb 27;348(9):791-9
12606733
Colorectal Dis. 2005 Jul;7(4):327-31
15932553
Int J Cancer. 2004 May 1;109(5):680-4
14999774
World J Gastroenterol. 2006 Feb 14;12(6):951-5
16521226
Int J Cancer. 2006 Apr 15;118(8):1937-40
16287072