3 research outputs found
Desmoid tumor: a disease opportune for molecular insights
Summary. Desmoid tumors are monoclonal
proliferations that fall within a broad histologic spectrum
of fibrous mesenchymal tumors that ranges from benign
proliferations of scar tissue to high-grade fibrosarcomas.
These low-grade tumors are extremely infiltrative
locally, but lack the ability to metastasize systemically.
While they are only rarely a direct cause of mortality,
using current therapeutic modalities, these tumors have a
high rate of local recurrence that can result in significant
treatment related morbidity. Sporadic desmoids are
usually associated with somatic mutations in codons 41
or 45 of exon 3 of ß-catenin (CTNNB1). Desmoid tumors
occurring in the background of familial adenomatous
polyposis (FAP) usually contain inactivating germline
mutations in the adenomatous polyposis coli (APC)
gene. CTNNB1 and APC are part of the Wnt signaling
pathway and mutations in either gene result in
stabilization of the ß-catenin protein and allow nuclear
translocation and binding of ß-catenin to the T-cell
factor/lymphoid enhancer factor (TCF/Lef) family of
transcription factors, resulting in activation of target
genes which may underlie desmoid tumor biology and
clinical behavior. In an era of molecularly targeted
therapeutics there is a real need to better grasp the
molecular mechanisms behind desmoid tumorigenesis
and progression. This knowledge will eventually result
in the development of patient and tumor tailored
therapies and assist in the control and eradication of this
disease