A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene
Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP) as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families.
Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. World health organization classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC, 2013:83-5.
Klemmer S, Pascoe L, DeCosse J. Occurrence of desmoids in patients with familial adenomatous polyposis of the colon. Am J Med Genet 1987;28:385-92.
Nieuwenhuis MH, De Vos Tot NederveenCappel W, Botma A, Nagengast FM, Kleibeuker JH, Mathus-Vliegen EM, et al. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol 2008;6:215-9.
Kalady MF, Church JM. Monitoring and Management of Desmoids and Other Extracolonic Manifestations in Familial Adenomatous Polyposis. Semin Colon Rectal Surg 2011;22:112-7.
Tudyka VN, Clark SK. Surgical treatment in familial adenomatous polyposis. Ann Gastroenterol 2012;25:201-6.
Trainer AH. Extra-colonic manifestations of familial adenomatous polyposis coli. Adv Exp Med Biol 2009;656:119-27.
Lynch HT, Smyrk T, McGinn T, Lanspa S, Cavalieri J, Lynch J, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer 1995;76:2427-33.
Teo HE, Peh WC, Shek TW. Case 84: desmoid tumor of the abdominal wall. Radiology 2005;236:81-4.
Schiessling S, Kihm M, Ganschow P, Kadmon G, Buchler MW, Kadmon M. Desmoidtumour biology in patients with familial adenomatous polyposis coli. Br J Surg 2013;100:694-703.
Couture J, Mitri A, Lagace R, Smits R, Berk T, Bouchard H, et al. A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor. Clin Genet 2000;57:205-12.
Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Boker T, et al. Familial adenomatous polyposis:desmoidtumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 1995;4:337-40.
Wachsmannova-Matelova L, Stevurkova V, Adamcikova Z, Holec V, Zajac V. Different phenotype manifestation of familial adenomatous polyposis in families with APC mutation at codon 1309. Neoplasma 2009;56:486-9.
Nieuwenhuis MH, Lefevre JH, Bulow S, Jarvinen H, Bertario L, Kerneis S, et al. Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study. Dis Colon Rectum 2011;54:1229-34.
Eccles DM, van der Luijt R, Breukel C, Bullman H, Bunyan D, Fisher A, et al. Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene. Am J Hum Genet 1996;59:1193-201.
De QueirozRossanese LB, De Lima Marson FA, Ribeiro JD, Coy CS, Bertuzzo CS. APC germline mutations in families with familial adenomatous polyposis. Oncol Rep 2013;30:2081-8.
Andresen PA, Heimdal K, Aaberg K, Eklo K, Ariansen S, Silye A, et al. APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations. J Cancer Res ClinOncol 2009;135:1463-70.
Spirio L, Olschwang S, Groden J, Robertson M, Samowitz W, Joslyn G, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993;75:951-7.
Nielsen M, Bik E, Hes FJ, Breuning MH, Vasen HF, Bakker E, et al. Genotype-phenotype correlations in 19 Dutch cases with APC gene deletions and a literature review. Eur J Hum Genet 2007;15:1034-42.
Kashfi SM, BehboudiFarahbakhsh F, Golmohammadi M, NazemalhosseiniMojarad E, Azimzadeh P, AsadzadehAghdaie H. Frameshift Mutations (Deletion at Codon 1309 and Codon 849) in the APC Gene in Iranian FAP Patients: a Case Series and Review of the Literature. Int J Mol Cell Med 2014;3:196-202.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.