Molecular Analysis of Desmoid Tumors with a High-Density Single-Nucleotide Polymorphism Array Identifies New Molecular Candidate Lesions

Abstract

Background: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. Patients and Methods: In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. Results: Single samples showed numerical aberrations on chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8 could be detected. Recurrent heterozygous deletions were found in Chr 5q (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding regions for the potential tumor suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. In addition, structural chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases. Conclusion: The genomic alteration affecting the candidate gene CSMD1 could be important in the development of desmoid tumors.

The Prognostic Role of β-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only

“…Studies were excluded for the following reasons: describing a pediatric cohort (n = 1), no CTNNB1 mutation type data available (n = 14), no full text available (n = 3), conference abstract (n = 1), no recurrence data described (n = 6), no DTF as main subject (n = 1), and a review article (n = 3). Based on the origin of the patient cohort, 8 studies had to be excluded for describing patient sets having a large overlap with series already published 19,24,25,29–33 . The papers describing the largest cohort were included to request the IPD.…”

“…Several studies could not be included in this meta-analysis due to potential cohort overlap and due to the impossibility to acquire the IPD. 15,19,[23][24][25][29][30][31][32][33][34][35] Although there might be a selection, this is the largest cohort describing the correlation between CTNNB1 mutation type and recurrence risk to date. Despite these limitations, using the IPD of several international cohorts created a large pooled cohort of patient that received the same treatment, unique for a rare disease like DTF.…”

“…Based on the origin of the patient cohort, 8 studies had to be excluded for describing patient sets having a large overlap with series already published. 19,24,25,[29][30][31][32][33] The papers describing the largest cohort were included to request the IPD. From others we were not able to receive the IPD.…”

AKT1 and BRAF mutations in pediatric aggressive fibromatosis

“…Aside from the CTNNB1 and APC mutations, the genetic profile of pediatric AF has been poorly characterized. A few molecular analyses have been performed on adult AF using comparative genomic hybridization or high‐density single‐nucleotide polymorphism array, and shown loss of 5q (including the APC locus), 6q and 8p23, but such studies are completely lacking in pediatric AF .…”

Molecular Characterization of Desmoid Tumors: Decryption of the Enigma

“…InthisissueofOnkologie,Erbenandcolleaguescomprehensively evaluate 9 patients with desmoid tumors of the abdomen(n=7)andextremity(n=2);8/9weresporadicdes-moids while 1 patient had familial adenomatous polyposis [13]. Resection only was the treatment for 4 patients while 5patientshadradiationtherapy,1patientchemotherapy,and 2 patients hormonal therapy.…”