Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72
Tóm tắt
Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP. With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.
Tài liệu tham khảo
Bjork J, Akerbrant H, Iselius L, Alm T, Hultcrantz R: Epidemiology of familial adenomatous polyposis in Sweden: changes over time and differences in phenotype between males and females. Scand J Gastroenterol. 1999, 34: 1230-5. 10.1080/003655299750024751.
Bulow S, Faurschou Nielsen T, Bulow C, Bisgaard ML, Karlsen L, Moesgaard F: The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996, 11: 88-91. 10.1007/BF00342466.
Kinzler KW, Nilbert MC, Su L-K, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Bogudski MS, Altschui SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y: Identification of FAP locus genes from chromosome 5q21. Science. 1991, 253: 661-665. 10.1126/science.1651562.
Goss KH, Groden J: Biology of the adnomatous polyposis coli tumor suppressor. J Clin Oncol. 2000, 18: 1967-79.
Beroud C, Soussi T: APC gene: Database of germline and somatic mutations in human tumors and cell lines. Nucl Acid Res. 1996, 24: 121-4. 10.1093/nar/24.1.121.
Ficari F, Cama A, Valanzano R, Curia MC, Palmirotta R, Aceto G, Esposito DL, Crognale S, Lombardi A, Messerini L, Mariana-Costantini R, Tonelli F, Battista P: APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis. Br J Cancer. 2000, 82: 348-53. 10.1054/bjoc.1999.0925.
Nieuwenhuis MH, Vasen HFA: Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): A review of the literature. Crit Rev Onc Hematol. 2007, 61: 153-61. 10.1016/j.critrevonc.2006.07.004.
Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, Gelbert L, Thliveris A, Carlson M, Otterud B, Lynch H, Watson P, Lynch P, Lurent-Puig P, Burt R, Hughes JP, Thomas G, Leppert M, White R: Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993, 75: 951-7. 10.1016/0092-8674(93)90538-2.
Soravia C, Berk T, Madlensky L, Mitri A, Cheng H, Gallinger S, Cohen Z, Bapat B: Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998, 62: 1290-301. 10.1086/301883.
Enomoto M, Konishi M, Iwama T, Utsunomiya J, Sugihara KI, Miyaku M: The relationship between frequencies of extracolonic manifestations and the position of the APC germline mutation in patients with familial adenomatous polyposis. Jpn J Clin Oncol. 2000, 30: 82-8. 10.1093/jjco/hyd017.
Nilbert M, Fernebro J, Kristoffersson U: Novel germline APC mutations in Swedish patients with familial adenomatous polyposis and Gardner syndrome. Scand J Gastroenterol. 2000, 35: 1200-3. 10.1080/003655200750056691.
Mueller J, Kanter-Smoler G, Nygren AO, Errami A, Grönberg H, Holmberg E, Björk J, Wahlström J, Nordling M: Identification of genomic deletions in the APC gene in familial adenomatous polyposis by two independent quantitative techniques. Genet Test. 2004, 8: 248-56. 10.1089/gte.2004.8.248.
Kanter-Smoler G, Fritzell K, Rohlin A, Engwall Y, Hallbeg B, Bergman A, Meuller J, Gronberg H, Karlsson P, Björk J, Nordling M: Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families. BMC Med. 2008, 6: 10-10.1186/1741-7015-6-10.
Bisgaard ML, Fenger K, Bülow S, Niebuhr E, Mohr J: Familal adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat. 1994, 3: 121-5. 10.1002/humu.1380030206.
Sieber OM, Lamlum H, Crabtree MD, Rowan AJ, Rowan AJ, Barclay E, Lipton L, Hodgson S, Thomas HJ, Neale K, Phillips RK, Farrington SM, Dunlop MG, Mueller HJ, Bisgaard ML, Bulow S, Fidalgo P, Albuquerque C, Scarano MI, Bodmer W, Tomlinson IP, Heinimann K: Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. PNAS. 2002, 99: 2954-8. 10.1073/pnas.042699199.
Sturt NJH, Gallagher MC, Bassett P, Philp CR, Neale KF, Tomlinson IP, Silver AR, Phillips RK: Evidence for genetic predisposition to desmoids tumors in familial adenomatous polyposis independent of the germline APC mutation. Gut. 2004, 53: 1832-6. 10.1136/gut.2004.042705.
Bülow S, Holm NV, Mellemgaard A: Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis. Int J Colorectal Cancer Dis. 1988, 3: 29-31. 10.1007/BF01649679.
Truta B, Allen BA, Conrad PG, Weinberg V, Miller GA, Pomponio R, Lipton LR, Guerra G, Tomlinson IP, Sleisenger MH, Kim YS, Terdima JP: Genotype and phenotype of patients with both familial adenomatous polyposis and thyroid carcinoma. Fam Cancer. 2003, 2: 95-9. 10.1023/A:1025762706854.
Brozek I, Plawski A, Podralska M, Kanka C, Slomski R, Limon J: Thyroid cancer in two siblings with FAP syndrome and APC mutation. Int J Colorectal Dis. 2008, 23: 331-2. 10.1007/s00384-007-0365-0.
Kameyama K, Takami H: FAP associated thyroid carcinoma in mother and her daughter. Fam Cancer. 2001, 1: 83-6. 10.1023/A:1013848307459.
Lee S, Hong SW, Shin SJ, Kim YM, Rhee Y, Jeon BI, Moon WC, Oh MR, Lim SK: Papillary thyroid carcinoma associated with familial adenomatous polyposis: molecular analysis of pathogenesis in a family and review of the literature. Endocrin J. 2004, 51: 317-23. 10.1507/endocrj.51.317.
Lyster Knudsen A, Bisgaard ML, Bulow S: Attenuated familial adenomatous polyposis (AFAP). Review of the literature. Fam Cancer. 2003, 2: 43-55. 10.1023/A:1023286520725.
Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, Kuwada SK, Neklason DW, Disario JA, Lyon E, Hughes JP, Chey WY, Whute RL: Genetic testing and phenotype in a large kindred with attenuated familial polyposis. Gastroenterology. 2004, 127: 444-51. 10.1053/j.gastro.2004.05.003.
Luijt Van der RB, Meera Khan P, Vasen HFA, Breukel C, Tops CM, Scott RJ, Fodde R: Germline mutations in the 3' part of APC exon 15 do not result in truncated proteins and are associated withe attenuated adenomatous polyposis coli. Hum Genet. 1996, 98: 727-34. 10.1007/s004390050293.
Young J, Simms LA, Tarish J, Buttenshaw R, Knight N, Anderson GJ, Bell A, Leggett B: A family with attenuated familial adenomatous polyposis due to a mutation in the alternatively spliced region of APC exon 9. Hum Mut. 1998, 11: 450-5. 10.1002/(SICI)1098-1004(1998)11:6<450::AID-HUMU5>3.0.CO;2-P.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/9/101/prepub