MYH Gene Status in Polish FAP Patients without APC Gene Mutations
Tóm tắt
Familial Adenomatous Polyposis (FAP) is an inheritable predisposition for the occurrence of numerous polyps in the large intestine. In about 50% of all patients, the occurrence of the disease is conditioned by heterozygotic mutations of the APC gene. Screening for genetic factors in persons without mutations in the APC gene led to the identification of homozygotic mutations of the MYH gene as the cause of the appearance of the polyposis form which is characterized by recessive heritability and a milder course than in the case of the classic form of the disease. The authors examined 90 persons from the DNA bank of patients with FAP from the Institute of Human Genetics of the Polish Academy of Sciences in Poznań in whom no mutations in the APC gene were detected. Two of the most frequent mutations of the MYH gene (Y165C and G382D) were found to be heterozygous in 13% of patients and no other mutations in this gene coding sequence were observed. In the group with heterozygotic occurrence of the mutation in the MYH gene, the disease phenotype was not milder in comparison with the entire examined group and the mean age of the disease manifestation was even lower. This observation allows one to conclude that the employed methods of mutation screening were correct and, in the case of the examined group, the mutation ratio of the MYH gene does not precondition the occurrence of the disease, but it cannot be excluded that it may modify its phenotype. The obtained results indicate that the criteria applied during the process of FAP qualification are more rigorous than those applied in other countries.
Tài liệu tham khảo
Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, Le Paslier D, Abderrahim H, Cohen D, Leppert M, White R: Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991, 66: 589–600. 10.1016/0092-8674(81)90021-0
Kinzler KW, Nilbert MC, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hamilton SR, Hedge P, Markham A, Carlson M, Joslyn G, Groden J, White R, Miki Y, Miyoshi Y, Nishisho I, Nakamura Y: Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 1991, 251: 1366–1370. 10.1126/science.1848370
Friedl W, Aretz S: Familial Adenomatous Polyposis: Experience from a Study of 1164 Urelated German Plyposis Patients. Hereditary Cancer in Clinical Practice 2005, 3: 87–114.
McGoldrick JP, Yeh YC, Solomon M, Essigmann JM, Lu AL: Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein. Mol Cell Biol 1995, 15: 989–996.
Cheadle JP, Sampson JR: Exposing the MYtH about base excision repair and human inherited disease. Hum Mol Genet 2003, 12: R159–165. 10.1093/hmg/ddg259
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP: Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 2003, 348: 791–799. 10.1056/NEJMoa025283
Al-Tassan N, Eisen T, Maynard J, Bridle H, Shah B, Fleischmann C, Sampson JR, Cheadle JP, Houlston RS: Inherited variants in MYH are unlikely to contribute to the risk of lung carcinoma. Hum Genet 2004, 114: 207–210. 10.1007/s00439-003-1033-2
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP: Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C--> T:A mutations. Hum Mol Genet 2002, 11: 2961–2967. 10.1093/hmg/11.23.2961
Plawski A, Lubinski J, Banasiewicz T, Paszkowski J, Lipinski D, Strembalska A, Kurzawski G, Byrski T, Zajaczek S, Hodorowicz-Zaniewska D, Gach T, Brozek I, Nowakowska D, Czkwaniec E, Krokowicz P, Drews M, Zeyland J, Juzwa W, Slomski R: Novel germline mutations in the adenomatous polyposis coli gene in Polish families with familial adenomatous polyposis. J Med Genet 2004, 41: e11. 10.1136/jmg.2003.010215
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP: Inherited variants of MYH associated with somatic G:C--> T:A mutations in colorectal tumors. Nat Genet 2002, 30: 227–232. 10.1038/ng828
Plawski A, Jura J, Slomski R: Wykrywanie mutacji punktowych w genie supresorowym APC człowieka metodą heterodupleksów. In Przykłady analiz DNA. Edited by: Słomski R. Wydawnictwo Akademii Rolniczej w Poznaniu; 2004:100–106.
Kairupan CF, Meldrum CJ, Crooks R, Milward EA, Spigelman AD, Burgess B, Groombridge C, Kirk J, Tucker K, Ward R, Williams R, Scott RJ: Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations. Int J Cancer 2005, 116: 73–77. 10.1002/ijc.20983