Keywords
Adenomatous polyposis coli (APC)
Gene mutation
Submitted : 2022-04-30
Accepted : 2022-05-15
Published : 2022-05-30
Abstract
Objective: To identify the causative adenomatous polyposis coli (APC) gene defects associated with a pedigree of familial adenomatous polyposis (FAP). Methods: FAP was diagnosed based on clinical manifestations, family history, as well as endoscopic and pathological examinations. The blood samples of the FAP pedigree members, colonic polyp patients, and normal individuals were collected. Genomic DNA was then extracted from those samples. APC mutation analysis was conducted via direct polymerase chain reaction (PCR) sequencing. Results: Three synonymous mutations and a missense mutation were found: c.5034G>A (p.Gly1678Gly), c.5465T>A (p.Val1822Asp), c.5880G>A (p.Pro1960Pro), and c.5274T>G (p.Ser1758Ser). Among them, the homozygous mutation on APC gene c.5034G>A has been reported, while the other three mutations have not been reported in the Chinese Han population. Individuals with c.5465T>A (p.Val1822ASP) missense mutation eventually suffer from colon cancer and have poor prognosis. We found no mutation in patients with simple intestinal polyp and in normal individuals. In addition, there were homozygous and heterozygous mutations in different patients from the same family. Conclusion: Three new mutations of APC gene were firstly reported in Han population. The missense mutation of c.5465T>A (p.Val1822Asp) may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.
References
Bussey HJR, 1975, Familial Polyposis Coli, John Hopkins University Press, Baltimore.
Reed TE, Neel JV, 1955, A Genetic Study of Multiple Polyposis of the Colon with An Appendix Deriving A Method of Estimating Relative Fitness. Am J Hum Genet, 7(3): 236-263.
Alm T, 1975, Surgical Treatment of Hereditary Adenomatosis of the Colon and Rectum in Sweden During the Last 20 Years. Part II. Patients with Prophylactic Operations, Primary and Late Results. Discussion and Summary. Acta Chir Scand, 141(3): 228-237.
Liu J, Zheng S, Feng C, et al., 1997, Registration and Report of Familial Polyposis Pedigree. Chinese Journal of Cance, 19(6): 416.
Bulow S, Faurschou Nielsen T, Bulow C, et al., 1996, The Incidence Rate of Familial Adenomatous Polyposis: Results from the Danish Polyposis Register. Int J Colorectal Dis, 11(2): 88-91.
Jarvinen HJ, 1992, Epidemiology of Familial Adenomatous Polyposis in Finland: Impact of Family Screening on the Colorectal Cancer Rate and Survival. Gut, 33(3): 357-360.
Half E, Bercovich D, Rozen P, 2009, Familial Adenomatous Polyposis. Orphanet Journal of Rare Diseases, 4: 22 DOI: 10.1186/1750-1172-4-22
Nishisho I, Nakamura Y, Miyoshi Y, et al., 1991, Mutations of Chromo¬some 5q21 Genes in FAP and Colorectal Cancer Patients. Science, 253(5020): 665-669.
Groden J, Thliveris A, Samowitz W, et al., 1991, Identification and Char¬acterization of the Familial Adenomatous Polyposis Coli Gene. Cell, 66(3): 589-600.
Kiider KW, Nilbert MC, Su LK, et al., 1991, Identification of FAP Locusgenes from Chromosome 5q21. Scinence, 235(5020): 661-665.
Akiyama T, Kawasaki Ym 2006, Wnt Signaling and the Actin Cytoskeleton. Oncogene, 25(57): 7538-44.
Aretz S, Stienen D, Friedrichs N, 2007, Somatic APC Mosaicism: A Frequent Cause of Familial Adenomatous Polyposis (FAP). Hum Mutat, 28(10): 985-992.
Song G, Yuan Y, Zheng F, Et Al., 2013, Novel Insertion Mutation p.Asp610GlyfsX23 in APC Gene Causes Familial Adenomatous Polyposis in Chinese Families Gene, 516(2): 204-208.
Leppert M, Burt R, Hughes JP, et al., 1990, Genetic Analysis of an Inherited Predisposition to Colon Cancer in A Family with A Variable Number of Adenomatous Polyps. N Engl J Med, 322(13): 904-908.
Nielsen M, Hes FJ, Nagengast FM, et al., 2007, Germline Mutations in APC and MUTYH are Responsible for the Majority of Families with Attenuated Familial Adenomatous Polyposis. Clin Genet, 71: 427-433.