Mutation spectrum of the APC gene in 83 Korean FAP families.
Familial adenomatous polyposis (FAP) is a clinically well-defined hereditary disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. FAP is characterized by polyposis in the large bowel and variable extracolonic manifestations. With an increase of reported APC germline mutations, many reports have investigated genotype-phenotype correlations in FAP patients. Here, we analyzed the APC gene for germline mutations in 83 unrelated Korean FAP patients and investigated genotype-phenotype correlations. We identified germline APC mutations in 59 (71%) of the cases, including 34 frameshift mutations, 19 nonsense mutations, and six splice site mutations. Among 59 patients with the identified germline mutation of the APC gene, 37 had been reported previously and were included in the genotype-phenotype analysis. In the other 22 patients, we identified seven novel mutations: c.1438C>T, c.2232_2233dupCT, c.3426delT, c.3739_3769del31, c.3931_3935delATTGG, c.4332dupA, and c.4722_4725delACTA. Desmoid tumors were identified in six of the examined FAP patients, five of whom had APC germline mutations; these mutations involved codons 849, 864, 1309, 1444 and 1464, respectively (c.2547_2548delTA, c.2592_2593insCT, c.3927_3931delAAAGA, c.4332dupA and c.4391-4394delAGAG). Four of the included FAP patients had papillary thyroid cancers; all were female and had germline APC mutations (c.1863_1865delTTAincCT, c.2805C>A, c.3183_3187delACAAA and c.3927_3931delAAAGA).
Kim
Duck-Woo
DW
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
Kim
Il-Jin
IJ
Kang
Hio Chung
HC
Park
Hye-Won
HW
Shin
Yong
Y
Park
Jae-Hyun
JH
Jang
Sang-Geun
SG
Yoo
Byong Chul
BC
Lee
Min Ro
MR
Hong
Chang Won
CW
Park
Kyu Joo
KJ
Oh
Nahm-Gun
NG
Kim
Nam Kyu
NK
Sung
Moo Kyung
MK
Lee
Bong Wha
BW
Kim
Young Jin
YJ
Lee
Hyucksang
H
Park
Jae-Gahb
JG
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D003062:Codon; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D017491:Genes, APC; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007723:Korea; D008297:Male; D008957:Models, Genetic; D009154:Mutation
D025601:Adenomatous Polyposis Coli Protein; D003062:Codon