Genomic alterations

Most desmoid tumors are sporadic, but a small proportion may occur in association with a variant in the APC gene (associated with intestinal polyps and a high incidence of colon cancer). In a study of 519 patients older than 10 years with a diagnosis of desmoid-type fibromatosis, 39 patients (7.5%, a possible underestimation) were found to have familial adenomatous polyposis (FAP).[3] The patients with FAP and desmoid-type fibromatosis were younger, more often male, and had more abdominal wall or mesenteric tumors than did patients with desmoid-type fibromatosis without FAP.

Variants in exon 3 of the CTNNB1 gene are seen in more than 80% of desmoid-type fibromatosis cases. The 45F variant in exon 3 of the CTNNB1 gene has been associated with an increased risk of disease recurrence.[4]

Currently, there are no general recommendations for genetic testing in children with desmoid-type fibromatosis. Pathological and molecular characteristics of the tumor only provide guidance for screening.

A patient should be referred to a genetic counselor if there is a family history of colon cancer, congenital hyperplasia of the retinal pigment epithelium is present,[5,6] or the desmoid-type fibromatosis occurs in the abdomen or abdominal wall.[3] If the tumor has a somatic CTNNB1 variant, screening is not necessary, because the APC gene variant has not been described in this setting. If a CTNNB1 variant is not identified, screening for the APC variant may be warranted.[7,8]

Pediatric desmoid tumors can harbor additional variants in the AKT, BRAF V600E, TP53, and RET genes.[9] For more information, see the Familial Adenomatous Polyposis (FAP) section in Genetics of Colorectal Cancer.