title: Identification of previously unrecognized FAP in children with Gardner fibroma.
abstract: Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present β-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for β-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.
authors: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors: Joana
authors: J
authors: Vieira
authors: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors: Carla
authors: C
authors: Pinto
authors: Department of Pathology, Portuguese Oncology Institute, Porto, Portugal.
authors: Mariana
authors: M
authors: Afonso
authors: Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal.
authors: Maria
authors: M
authors: do Bom Sucesso
authors: Department of Pathology, Portuguese Oncology Institute, Porto, Portugal.
authors: Paula
authors: P
authors: Lopes
authors: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors: Manuela
authors: M
authors: Pinheiro
authors: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors: Isabel
authors: I
authors: Veiga
authors: 1] Department of Pathology, Portuguese Oncology Institute, Porto, Portugal [2] Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
authors: Rui
authors: R
authors: Henrique
authors: 1] Department of Genetics, Portuguese Oncology Institute, Porto, Portugal [2] Institute of Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
authors: Manuel R
authors: MR
authors: Teixeira
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D004252:DNA Mutational Analysis; D005260:Female; D005350:Fibroma / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin