Abstract 5756: Next-generation sequencing (NGS) reveals different molecular profiles of pediatric sarcoma in children and adults

Abstract

Abstract Background: Pediatric sarcomas represent approximately 12% of all pediatric cancers with over 100 subtypes. Although some molecular detection techniques can be used to assist the diagnosis and treatment of pediatric sarcoma, it still remains challenging due to overlapping morphological features and limited biopsy specimens. Here we performed next generation sequencing (NGS) to analyze the molecular profiles of pediatric and adult sarcomas in China. Methods: A total of 700 Chinese patients with sarcoma were collected. The tumor tissue and matching blood specimens were tested by the integrative DNA and RNA sequencing panel Onco Panscan plus࣪ at Genetronhealth. Results: Of the 700 sarcoma patients, there were 224 children (32%) and 476 adults (68%). Difference from the almost same ratio of men to women in adults, there were more males (n = 134) than females (n = 90) in children. Rhabdomyosarcoma was the most common soft tissue tumor in children, accounting for 24.1% (n = 54), followed by Ewing's sarcoma (9.8%, n = 22) and Osteosarcoma (8.5%, n = 34), while Angiosarcoma (3.8%, n = 18) and Fibrosarcoma (3.6%, n = 17) were the most common in adults. Based on mutation types, the frequent alterations were missense mutations (n = 326, 51.2%), fusions (n = 129, 20.3%) and copy number variants (n = 66, 10.4%) in children with a mean of 3 mutations per patient, and missense mutations (n = 1438, 66.8%), fusions (n = 221, 10.3%) and truncating mutations (n = 215, 10.0%) in adults with an average 5 mutations. TP53 (12.9%, n = 29), EWSR1 (8.9%, n = 20) and ALK mutations (6.7%, n = 15) were common in children, which was distinct from TP53 (29.4%, n = 140), NF1 (4.8%, n = 23), CTNNB1 (4.2%, n = 20) and RB1 (4.2%, n = 20) in adults. Based on NGS results, pathological subtypes could be confirmed in 40.2% (90/224) and 48.1% (229/476) of children and of adults sarcoma patients, respectively. In addition, we identified a total of 72 drug-targeted gene mutations in the 57 children patients, of which 35 (48.6%) gene mutations could be targeted by FDA-approved drugs. In adults, 256 drug-targeted gene mutations were detected and the proportion of actionable mutations was up to 78.9% (n = 202). Conclusion: The genomic landscape of pediatric sarcomas is different from that of adults. NGS aids in the subtype classification and clinical guidance of pediatric sarcomas, providing evidence for personalized treatments with clinical benefit. Citation Format: Weisong Cai, Fang Liu, Xuejiao Liu, Xiaojuan Wang, Chunyang Wang, Tonghui Ma, Shu Li. Next-generation sequencing (NGS) reveals different molecular profiles of pediatric sarcoma in children and adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5756.