Division of Cellular Signaling, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Eur J Cancer. 2021 Mar;145:109-120. doi: 10.1016/j.ejca.2020.12.001. Epub 2021 Jan 11.
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). 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.
先前的研究并未明确确定硬纤维瘤（DT）的预后因素。对 64 例 DT 进行了全外显子组测序（WES）和/或 RNA 测序（RNA-seq），以结合临床病理特征研究分子谱。在 56 例（87.5%）中鉴定出具有特定热点的 CTNNB1 突变。在 14 例（21.9%）中鉴定出染色体 6（chr6）的拷贝数丢失。基于 mRNA 表达谱的聚类可预测患者的预后。由三个基因集（IFI6、LGMN 和 CKLF）表达产生的风险评分是本队列中无复发生存（RFS）的强预后标志物。在按 IFI6 表达分层的风险组中，高风险组相对于低风险组的无复发生存危险比为 12.12（95%置信区间：1.56-94.2；p=8.0×10）。总之，CTNNB1 突变和 chr6 拷贝数丢失可能是 DT 肿瘤发生的致病突变，而基因表达谱可能有助于区分适合观察等待管理的患者和可能受益于额外的系统或放射治疗的患者。
