Familial Adenomatous Polyposis-Associated Desmoids Display Significantly More Genetic Changes than Sporadic Desmoids

Abstract

Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression.

A Prognostic Nomogram for Prediction of Recurrence in Desmoid Fibromatosis

“…1, 2 Desmoids are associated with β-catenin mutations in over 75% of cases; a smaller proportion are associated with APC mutations and familial adenomatous polyposis. 3-7 The lesions do not have the ability to metastasize, but progressive disease and local recurrence can lead to significant morbidity. 8 Intraabdominal tumors may cause intestinal obstruction or fistulization and extremity tumors may result in neuropathic pain and limited mobility.…”

Prognostic factors for the recurrence of sporadic desmoid-type fibromatosis after macroscopically complete resection: Analysis of 114 patients at a single institution

“…2,3 Most cases of the disease are sporadic and are genetically associated with Wnt/b-catenin pathway gene mutations, though a small proportion is associated with APC gene mutations and familial adenomatous polyposis (FAP). 4,5 The growth pattern is infiltrative and nonencapsulated, which makes local remission very difficult. Although the survival prognosis of the tumor remains good overall, a reported high recurrence rate of 24e77% and the subsequent treatment sequelae can lead to significant morbidity.…”

Desmoid Fibromatosis Presenting as Deep Venous Thrombosis: A Case Report and Discussion

“…They are most prevalent in patients 15–60 years of age, with peak incidence at age 30 years [6–10,14]. …”