The Desmoid Tumor Research Foundation

December 2022

Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor

Author Information

Ning B (1), Huang P (1), Zhu L (2), Ma Z (3), Chen X (4), Xu H (3), Ma R (1,2), Yao C (5), Zheng P (6), Xia T (7), Xia H (8).

(1) Department of Paediatric Orthopedics, Children's Hospital of Fudan University, Shanghai, 201102, China. (2) Department of Paediatric Orthopedics, Hainan Women and Children's Medical Center, Haikou, 570206, China. (3) Department of Pathology, Nanjing Drum Tower Hospital & Drum Tower Clinical College & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, 211166, China. (4) Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China. (5) Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University& Jiangsu Institute of Cancer Research, Nanjing, 2100092, China. yaochengyun@jszlyy.com.cn. (6) Department of Orthopedics Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. zhengpengfei@njmu.edu.cn. (7) Department of Paediatric Orthopedics, Children's Hospital of Fudan University, Shanghai, 201102, China. xiatian@fudan.edu.cn. (8) Department of Pathology, Nanjing Drum Tower Hospital & Drum Tower Clinical College & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, 211166, China. xiahongping@njmu.edu.cn.

Publication

Biol Proced Online

Summary

Background: Desmoid tumor (DT), also known as desmoid-type fibromatosis (DTF) or aggressive fibromatosis (AF) is a rare mesenchymal tumor affecting both children and adults. It is non-metastasis but infiltrative, growing with a high recurrence rate to even cause serious health problems. This study investigates the biology of desmoid tumors through integrated multi-omics studies. Methods: We systematically investigated the clinical data of 98 extra-abdominal cases in our pediatric institute and identified some critical clinical prognostic factors. Moreover, our integrated multi-omics studies (Whole Exome Sequencing, RNA sequencing, and untargeted metabolomics profiling) in the paired PDT tumor/matched normal tissues identified more novel mutations, and potential prognostic markers and therapeutic targets for PDTs. Results: The top mutation genes, such as CTNNB1 (p.T41A and p.S45F) and MUC4 (p.T3775T, p.S3450S, etc.), were observed with a mutation in more than 40% of PDT patients. We also identified a panel of genes that are classed as the FDA-approved drug targets or Wnt/β-catenin signaling pathway-related genes. The integrated analysis identified pathways and key genes/metabolites that may be important for developing potential treatment of PDTs. We also successfully established six primary PDT cell lines for future studies. Conclusions: These studies may promote the development of novel drugs and therapeutic strategies for PDTs.

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