Abstract
Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.