Linked Life Data

10782927

Source:http://linkedlifedata.com/resource/pubmed/id/10782927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-6-28
pubmed:abstractText
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 the disease 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 tumor also 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0009-9163
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
205-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10782927-3' Untranslated Regions, pubmed-meshheading:10782927-Adolescent, pubmed-meshheading:10782927-Adult, pubmed-meshheading:10782927-Aged, pubmed-meshheading:10782927-Alleles, pubmed-meshheading:10782927-Base Sequence, pubmed-meshheading:10782927-Blotting, Western, pubmed-meshheading:10782927-Colonic Neoplasms, pubmed-meshheading:10782927-Cytoskeletal Proteins, pubmed-meshheading:10782927-DNA Mutational Analysis, pubmed-meshheading:10782927-Family Health, pubmed-meshheading:10782927-Female, pubmed-meshheading:10782927-Fibromatosis, Aggressive, pubmed-meshheading:10782927-Genes, APC, pubmed-meshheading:10782927-Germ-Line Mutation, pubmed-meshheading:10782927-Humans, pubmed-meshheading:10782927-Immunohistochemistry, pubmed-meshheading:10782927-Male, pubmed-meshheading:10782927-Middle Aged, pubmed-meshheading:10782927-Molecular Sequence Data, pubmed-meshheading:10782927-Pedigree, pubmed-meshheading:10782927-Phenotype, pubmed-meshheading:10782927-Skin Neoplasms, pubmed-meshheading:10782927-Trans-Activators, pubmed-meshheading:10782927-beta Catenin
pubmed:year
2000
pubmed:articleTitle
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.
pubmed:affiliation
Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada. jcouture@mtsinai.on.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't