Precision Medicine Program in Chinese Pediatric Patients With Sarcoma.

Abstract

Molecular profiles of sarcomas in Chinese children remain unknown. The Chinese Pediatric Precision Oncology Group (CPPOG) is a prospective precision medicine program aimed at defining tumor molecular profiles in pediatric oncology patients across China, which aids diagnosis and treatment decisions. Herein, we report, to our knowledge, the first data from the CPPOG trial. Panel sequencing (830-gene DNA panel and 395-gene RNA panel) was performed on 214 tumors from 210 patients with sarcoma from 11 centers, between April 2021 and January 2022 in China. This study was prospectively analyzed to characterize subtype-specific somatic alterations and pathways. Molecular features among subgroups concerning response to treatment and pathologic characteristics were also identified. Genomic profiling revealed molecular aberrations in the patients: 88.3% harbored at least one somatic or germline alteration; 51.4% carried gene fusions (including 37 novel fusion variants); 46.3% possessed actionable therapeutic targets; 9.5% exhibited germline variants; and 14.3% had modified diagnoses based on molecular findings. In this study, the most common genetic alterations were <i>TP53</i> mutation and <i>EWSR1-FLI1</i> fusion. The most common activated pathways were TP53, PI3K, and RTK-RAS in pediatric sarcomas. Anaplastic embryonal rhabdomyosarcomas had special molecular characteristics, with high <i>TP53</i>, <i>MYCN</i>, and <i>MYCL</i> gene alteration frequencies. The mutation frequencies of <i>TP53</i> and <i>NRAS</i> were notably higher in patients who had undergone disease progression, relapse, or metastasis. Moreover, <i>MYC</i>, <i>MYCN</i>, and <i>MDM2</i> alterations were more frequent in tumors with mitotic figures >50/3 mm². Our study reveals the preliminary molecular landscape of Chinese pediatric sarcomas, indicating that molecular changes may represent different therapeutic responses and pathologic characteristics may correlate with molecular characteristics, suggesting the need for panel sequencing for pediatric sarcoma.