Abstract A011: Comprehensive molecular characterization of pediatric solid tumors in China: Findings from the Thousand Stars Precision Oncology Project

Background: Pediatric solid tumors represent a leading cause of cancer-related morbidity and mortality among children and adolescents. Precision oncology is widely used in adults but still limited in children. In 2018, we launched the 'Thousand Stars Precision Oncology Project' - a national program for genomic profiling and personalized treatment of childhood solid tumors in China. Methods: This study included 740 patients under the age of 21 diagnosed with solid tumors. Among them, 160 underwent whole-exome sequencing (WES), covering 20,000 genes, while 580 received targeted sequencing using a 706-gene panel. Clinical data, somatic and germline variants, tumor mutation burden (TMB), and potentially actionable alterations were comprehensively analyzed. Results: The median age was 12 years (range: 0–21) with 60.9% male. In the WES cohort, bone tumors were predominant (70.0%), followed by soft tissue tumors (10.0%) and renal tumors (8.8%). In the panel cohort, soft tissue tumors accounted for 36.2%, bone tumors for 36.2%, and renal tumors for 4.3%. In the WES group, the average number of somatic mutations per patient was 69.2 (range: 0–1936), with a mean TMB of 2.2. TMB >10 mutations/Mb was observed in 2.5% of patients. The average number of non-VUS mutations was 6.8, and 43% of patients carried at least one clinically significant variant. In the panel group, the average mutation count was 10.4 (range: 0–271), mean TMB was 4.2, and 3.1% had TMB >10. The average number of non-VUS mutations was 6.4, with 53% of patients harboring at least one clinically meaningful alteration. The most frequently mutated genes in the WES cohort were TP53 (33.8%), VEGFA (16.9%), NCOR1 (16.2%), CCND3 (12.5%), and XPO5 (11.9%). In the panel group, the top altered genes were TP53 (21.7%), CDKN2A (10.2%), NCOR1 (8.8%), EWSR1(8.6%), and VEGFA (7.6%). Importantly, a substantial number of patients harbored alterations with therapeutic implications, including BRCA1/2 alterations (19 patients), EGFR alterations (16 patients), NTRK1/2/3 fusions (28 patients), ERBB2 alterations (9 patients), and ALK fusions (9 patients). These findings provided a molecular basis for targeted therapy in select cases. Several patients showed good responses to targeted therapies based on these findings. Germline pathogenic or likely pathogenic variants were detected in 9.9% of patients (73/740), involving cancer susceptibility genes such as TP53, FANCA, BRCA1/2, NF1, BLM, and SPINK1, indicating a hereditary predisposition in a subset of this population. Conclusion: This study presents a comprehensive molecular characterization of pediatric solid tumors in a large Chinese cohort. The high prevalence of clinically significant and potentially targetable mutations underscores the relevance of incorporating genomic profiling into clinical care for pediatric patients. In addition, germline variants also show the need for family genetic counseling and monitoring. These findings advance pediatric precision oncology and support future therapeutic development for this underserved population. Citation Format: Qing Hao, Shaohua Yuan, Chengyi Wang, Xinxiu Meng, Zanmei Xu, Yannan Zhu, Kai Wang. Comprehensive molecular characterization of pediatric solid tumors in China: Findings from the Thousand Stars Precision Oncology Project [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr A011.