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OPAC HELP

Titolo:
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
Autore:
Couture, J; Mitri, A; Lagace, R; Smits, R; Berk, T; Bouchard, HL; Fodde, R; Alman, B; Bapat, B;
Indirizzi:
Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp Toronto ON Canada M5G 1X5 Surg, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada Mt SinaiHosp Toronto ON Canada M5G 1X5 Med, Toronto, ON M5G 1X5, Canada Univ Toronto, Samuel Lunenfeld Res Inst, Ctr Canc Genet, Toronto, ON, Canada Univ Toronto Toronto ON Canada Inst, Ctr Canc Genet, Toronto, ON, Canada Univ Toronto, Hosp Sick Children, Dept Surg, Toronto, ON M5G 1X8, Canada Univ Toronto Toronto ON Canada M5G 1X8 Surg, Toronto, ON M5G 1X8, Canada Univ Laval, Hotel Dieu, Dept Surg, Quebec City, PQ, Canada Univ Laval Quebec City PQ Canada ieu, Dept Surg, Quebec City, PQ, Canada Univ Laval, Hotel Dieu, Dept Pathol, Quebec City, PQ, Canada Univ Laval Quebec City PQ Canada u, Dept Pathol, Quebec City, PQ, Canada Leiden Univ, Dept Human Genet, MGC, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands
Titolo Testata:
CLINICAL GENETICS
fascicolo: 3, volume: 57, anno: 2000,
pagine: 205 - 212
SICI:
0009-9163(200003)57:3<205:AGMATE>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL ADENOMATOUS POLYPOSIS; LINE MUTATIONS; COLI; PROTEIN;
Keywords:
beta-catenin; desmoid tumors; familial polyposis; phenotype; 3 ' APC mutation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Couture, J Mt Sinai Hosp, Dept Surg, 600 Univ Ave,Suite 1225, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp 600 Univ Ave,Suite 1225 Toronto ON Canada M5G1X5
Citazione:
J. Couture 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, 57(3), 2000, pp. 205-212

Abstract

Desmoid tumors arise sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis (FAP). In FAP, two distinct clinical presentations of the desmoid phenotype are seen: 1) one or a few desmoid tumors present predominantly in the abdominal wall or the abdomen; 2) a florid proliferation of tumors early in life, mostly near the axial skeleton or extremities. These different phenotypes have been associated with different sites of germline mutations in the adenomatous polyposis coli gene (APC gene). We present a large, French-Canadian kindred with a florid desmoid tumor phenotype caused by a germline mutation at codon 2643-2644 of the APC gene. The phenotype was characterized by the early onset of multiple tumors, arising near the axial skeleton and in proximal extremities. The penetrance of desmoid tumors was near 100% in this kindred. However, the expression of thedisease was variable amongst the different affected relatives. Many gene carriers had cutaneous cysts. Polyposis of the colon was rarely observed in the affected individuals and we did not document upper gastro-intestinal polyps. The mutant APC allele did not express a stable truncated protein in vivo. Molecular analysis of the proband's tumor DNA revealed a somatic inactivating mutation of the wild-type allele. Immunohistochemistry on the tumoralso demonstrated elevated levels of beta-catenin. The present study demonstrates that this extreme 3' APC mutation is associated with a severely penetrant desmoid phenotype and attenuated polyposis coli. It also suggests the involvement of the beta-catenin pathway in the development of desmoid tumors in FAP. The natural history of the disease is variable between individuals, and surgical interventions have to be timed appropriately due to the frequent recurrences.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:13:30