A novel 3′ mutation in the APC gene in a family presenting with a desmoid tumour

E ditor -Desmoid tumours, also known as infiltrative fibromatoses, are rare benign tumours which often recur after local resection and can cause death through local infiltration of vital structures. 1 The estimated incidence in the general population of such tumours is 1-2 per million but in familial adenomatous polyposis (FAP) they occur in up to 15% of cases. 2 Likely precipitating factors include trauma and female sex hormones, since females are more often affected than males. 3 The majority of desmoid tumours in FAP (over 90%) arise in the mesentery of the bowel or in the abdominal wall musculature. Discussion Classical familial adenomatous polyposis coli (FAP) is recognised by the presence of many hundreds of colonic adenomas throughout the colon. Since the identification of the gene responsible for FAP in 1991, it has been possible to recognise certain genotype/phenotype correlations which may not only allow the clinician to direct the molecular geneticist towards the most likely region where a mutation may be located, but conversely may predict the likely natural course of the disease associated with a given mutation and direct management strategies accordingly. 7 Where mutations fall into the 5[variant prime] and 3[variant prime] extremes of the gene, an attenuated colonic phenotype is usually seen with fewer and later onset polyps. 8 Whereas mutations at the 5[variant prime] end of the gene (exons 1-4) are not associated with desmoid tumour development, mutations arising in the 3[variant prime] half of the gene are more often associated with desmoid tumours, and in rare families this is the dominant phenotype with little else to suggest the diagnosis of polyposis on examination of the colon. 3 5 Although cytogenetic analysis of desmoid tumours is technically difficult and requires fresh tumour tissue, it may be a useful additional investigation where the phenotype for FAP is absent.