1. Comprehensive molecular and clinicopathological profiling of desmoid tumours.
- Author
-
Kohsaka S, Hirata M, Ikegami M, Ueno T, Kojima S, Sakai T, Ito K, Naka N, Ogura K, Kawai A, Iwata S, Okuma T, Yonemoto T, Kobayashi H, Suehara Y, Hiraga H, Kawamoto T, Motoi T, Oda Y, Matsubara D, Matsuda K, Nishida Y, and Mano H
- Subjects
- Adolescent, Adult, Aged, Chemokines genetics, Child, Preschool, Chromosomes, Human, Pair 6, Cysteine Endopeptidases genetics, DNA Mutational Analysis, Female, Fibromatosis, Aggressive mortality, Fibromatosis, Aggressive pathology, Fibromatosis, Aggressive therapy, Gene Dosage, Gene Expression Profiling, Humans, MARVEL Domain-Containing Proteins genetics, Male, Middle Aged, Mitochondrial Proteins genetics, Mutation, Prognosis, RNA-Seq, Tokyo, Exome Sequencing, Young Adult, beta Catenin genetics, Biomarkers, Tumor genetics, Fibromatosis, Aggressive genetics, Transcriptome
- Abstract
Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56-94.2; p = 8.0 × 10
6 ). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies., Competing Interests: Conflict of interest statement The authors certify that no actual or potential conflict of interest in relation to this article exists., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF