[32] Radiation Induced Sarcomas Occurring in Desmoid-Type Fibromatosis Are Not Derived from the Primary Tumour

Anne-Marie Cleton-Jansen, Pauline M Wijers-Koster, Cheryl M Coffin, Brian P Rubin, Judith VMG Bovee. LUMC, Leiden, Netherlands; Vanderbilt University, Nashville, TN; Taussig Cancer Center and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH

Background: Desmoid-type fibromatosis (ICD-O 8821/1) is a rare highly infiltrative and locally destructive neoplasm which does not metastasize, but may recur in 19-36% of the cases. They may occur in the context of familial adenomatous polyposis (FAP) which is caused by a mutation in the adenomatous polyposis gene (APC). APC mutations result in activation of the Wnt/β-catenin pathway. An alternative mechanism for activation is a mutation in exon 3 of CTNNB1, the gene encoding β-catenin, which results in stabilization of the protein. CTNNB1 mutations occur in 85% of the sporadic desmoid tumours. These locally aggressive lesions are preferably treated by surgery with a wide margin. If surgery is not possible radiation therapy is often used. In rare cases this may result in the development of a radiation induced sarcomawithin the treatment area. It is unclear whether these sarcomas develop from the primary tumour or arise de novo in normal tissue.
Design: To assess this issue we determined whether postradiation sarcomas arising in desmoid-type fibromatosis contain mutations in CTNNB1. We have collected four cases and determined the DNA sequence of exon 3 in the desmoid tumour and the subsequent postradiation sarcoma.
Results: In 2 out of 4 cases a T41A activating mutation in CTNNB1 could only be detected in the desmoid tumor, whereas in the radation induced osteosarcomas developing 6 and 11 years after treatment no CTNNB1 mutation was detected. A third case showed the S45F hotspot mutation in the original fibromatosis, whereas the postradiation undifferentiated sarcoma developing 6 years later was wildtype for CTNNB1 exon 3. The fourth case showed the T41A mutation in both in the desmoid fibromatosis as well as in a fibrosarcoma arising within the desmoid tumor.
Conclusions: In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis preferentially arise de novo and are not derived from the original desmoid tumour. Fibrosarcoma arising after this treatment may be derived from the original desmoid fibromatosis.
Category: Bone & Soft Tissue

Monday, March 4, 2013 1:00 PM

Poster Session II # 20, Monday Afternoon


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