Abstract
Colorectal cancer has become the third leading cause of death from cancer in Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of multiple adenomatous polyps in the colon and rectum. The gene responsible for FAP(APC) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30–80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554–1556, which created a downstream stop codon (codon 1558). This study is the first to report mutation analysis in Taiwanese FAP probands.
This is a preview of subscription content, log in via an institution to check access.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
References
Baba S. Familial cancer: Recent advances (in Japanese). Gan To Kagaku Ryoho 26:735–743;1999.
Bisgaard ML, Fenger K, Bulow S, Niebuhr E, Mohr J. Familial adenomatous polyposis (FAP): Frequency, penetrance, and mutation rate. Hum Mutat 3:121–125;1994.
Breukel C, Tops C, van Leeuwen C, van der Klift H, Fodde R, Khan PM. AT repeat polymorphism at the D5S122 locus tightly linked to adenomatous polyposis coli (APC). Nucleic Acids Res 19:6665;1991.
Cao X, Eu KW, Seow-Choen F, Cheah PY. Germline mutations are frequent in the APC gene but absent in the beta-catenin gene in familial adenomatous polyposis patients. Genes Chromosomes Cancer 25:396–398;1999.
Cao X, Eu KW, Seow-Choen F, Zao Y, Cheah PY. APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients. Eur J Hum Genet 8:42–48;2000.
Cruz-Bustillo D, Villasana L, Llorente F, et al. Preliminary results of the molecular diagnosis of familial adenomatous polyposis in Cuban families. Int J Colorectal Dis 17:344–347;2002.
Dobbie Z, Muller H. Germline mutations in the beta-catenin gene are not associated with the FAP phenotype without an APC mutation. J Med Genet 36:573–574;1999.
Dunlop MG. Screening for large bowel neoplasms in individuals with a family history of colorectal cancer. Br J Surg 79:488–494;1992.
Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet 10:721–733;2001.
Ficari F, Cama A, Valanzano R, et al. APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis. Br J Cancer 82:348–353;2000.
Gavert N, Yaron Y, Naiman T, et al. Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations. Hum Mutat 19:664;2002.
Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600;1991.
Gryfe R, Swallow C, Bapat B, Redston M, Gallinger S, Couture J. Molecular biology of colorectal cancer. Curr Probl Cancer 21:233–300;1997.
Department of Health, Taiwan. Health and Vital Statistics Taiwan area, ROC, 2001.
Hodgson SV, Coonar AS, Hanson PJ, et al. Two cases of 5q deletions in patients with familial adenomatous polyposis: Possible link with Caroli's disease. J Med Genet 30:369–375;1993.
Huber CG, Oefner PJ, Bonn GK. High-resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers. Anal Biochem 212:351–358;1993.
Hutter P, Rey-Berthod C, Chappuis PO, et al. Molecular and clinical characteristics in 32 families affected with familial adenomatous polyposis. Hum Mutat 18:550;2001.
Kinzler KW, Nilbert MC, Su LK, et al. Identification of FAP locus genes from chromosome 5q21. Science 253:661–665;1991.
Kohoutova M, Stekrova J, Jirasek V, Kapras J. APC germline mutations identified in Czech patients with familial adenomatous polyposis. Hum Mutat 19:460–461;2002.
Laken SJ, Papadopoulos N, Petersen GM, et al. Analysis of masked mutations in familial adenomatous polyposis. Proc Natl Acad Sci USA 96:2322–2326;1999.
Lindgren V, Bryke CR, Ozcelik T, Yang-Feng TL, Francke U. Phenotypic, cytogenetic, and molecular studies of three patients with constitutional deletions of chromosome 5 in the region of the gene for familial adenomatous polyposis. Am J Hum Genet 50:988–997;1992.
Matsumoto T, Iida M, Kobori Y, Mizuno M, Nakamura S, Hizawa K. Progressive duodenal adenomatosis in a familial adenomatous polyposis pedigree with APC mutation at codon 1556. Dis Colon Rectum 45:229–233;2002.
Matsumoto T, Iida M, Kobori Y, et al. Serrated adenoma in familial adenomatous polyposis: Relation to germline APC gene mutation. Gut 50:402–404;2002.
Mihalatos M, Danielides I, Belogianni J, et al. Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients. Cancer Genet Cytogenet 141:65–70;2003.
Moisio AL, Jarvinen H, Peltomaki P. Genetic and clinical characterisation of familial adenomatous polyposis: A population based study. Gut 50:845–850;2002.
Pang CP, Fan DS, Keung JW, et al. Congenital hypertrophy of the retinal pigment epithelium and APC mutations in Chinese with familial adenomatous polyposis. Ophthalmologica 215:408–411;2001.
Petersen GM, Boyd PA. Gene tests and counseling for colorectal cancer risk: Lessons from familial polyposis. J Natl Cancer Inst Monogr (17):67–71;1995.
Petersen GM, Slack J, Nakamura Y. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology 100:1658–1664;1991.
Resta N, Stella A, Susca F, et al. Nine novel APC mutations in Italian FAP patients. Hum Mutat 17:434–435;2001.
Sieber OM, Lipton L, Crabtree M, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799;2003.
Soussi T. UMD APC mutation database. Available at http://www.umd.necker.fr/, 2003.
Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 58:1130–1134;1998.
Toyooka M, Konishi M, Kikuchi-Yanoshita R, Iwama T, Miyaki M. Somatic mutations of the adenomatous polyposis coli gene in gastroduodenal tumors from patients with familial adenomatous polyposis. Cancer Res 55:3165–3170;1995.
Wu G, Wu W, Hegde M, et al. Detection of sequence variations in the adenomatous polyposis coli (APC) gene using denaturing high-performance liquid chromatography. Genet Test 5:281–290;2001.
Young J, Barker M, Fraser L, et al. Mutation searching in colorectal cancer studies: Experience with a denaturing high-pressure liquid chromatography system for exon-by-exon scanning of tumour suppressor genes. Pathology 34:529–533;2002.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wei, SC., Su, YN., Tsai-Wu, JJ. et al. Genetic analysis of the APC gene in taiwanese familial adenomatous polyposis. J Biomed Sci 11, 260–265 (2004). https://doi.org/10.1007/BF02256569
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02256569