Molecular characterization by array comparative genomic hybridization and DNA sequencing of 194 desmoid tumors

Desmoid tumors are fibroblastic/myofibroblastic proliferations. Previous studies reported that CTNNB1 mutations were detected in 84% and that mutations of the APC gene were found in several cases of sporadic desmoid tumors lacking CTNNB1 mutations. Forty tumors were analyzed by comparative genomic hybridization (CGH). Karyotype and fluorescence in situ hybridization revealed a nonrandom occurrence of trisomy 8 associated with an increased risk of recurrence. We report the first molecular characterization including a large series of patients. We performed array CGH on frozen samples of 194 tumors, and we screened for APC mutations in patients without CNNTB1 mutation. A high frequency of genomically normal tumors was observed. Four relevant and recurrent alterations (loss of 6q, loss of 5q, gain of 20q, and gain of Chromosome 8) were found in 40 out of 46 tumors with chromosomal changes. Gain of Chromosomes 8 and 20 was not associated with an increased risk of recurrence. Cases with loss of 5q had a minimal common region in 5q22.5 including the APC locus. Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome. A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/beta-catenin pathway.