Comprehensive understanding of genomic profile of bone cancer by the combination of DNA and RNA detection.

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e23513 Background: The diagnosis of bone tumors is mainly based on clinical manifestations, imaging examination, tissue biopsy and laboratory examination. However, most of the bone tumors have no specific clinical manifestations, which makes the diagnosis and differential diagnosis difficult. The genomic profile of bone tumor is helpful to provide molecular basis for its molecular diagnosis. Methods: A total of 357 Chinese bone cancer patients were enrolled in this study. The NGS-based YuanSu S panel which includes both DNA and RNA detection was performed by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: The 357 Chinese bone cancer patients were enrolled, including 206 adult patients and 151 juvenile patients, with a median age of 20 years old (ranged from 1 to 88 years). Among them, there were 214 males and 143 females. The most commonly mutated genes with a mutation frequency more than 10% were TP53 (31.65%), NCOR1 (15.69%), VEGFA (13.73%), RB1 (12.61%), CCND3 (11.76%), CDKN2A, GID4, and CCNE1 (11.48%, for each), TERT (10.64%), and MAP2K4 (10.08%). Germline mutations were detected in 28 patients, including 13 patients with HRD related mutations, such as ATM, FANCA, BRCA2, RAD50, RAD51D and FANCD2. A total of 179 gene fusions were detected in 130 bone cancer patients. Notably, 19 gene fusions such as SH2D2A-NTRK1, EMILIN1-ALK, and SZRD1-SPEN, were detected in 16 patients with the assistance of RNA detection. Statistical analysis showed that the mutations of NCOR1 (P = 1.1X10-4), VEGFA (P = 3.4X10-6), CCND3 (P = 1.0X10-5), GID4 (P = 1.1X10-6), CCNE1 (P = 3.0X10-7), RB1 (P = 0.03), and MAP2K4 (P = 1.5X10-4)were significantly associated with juvenile patient group, as well as the mutation of H3F3A (P = 7.5X10-5) was significantly associated with adult patient group. Conclusions: Here we identified the mutational characteristics of Chinese bone tumor patients. In addition, the inclusion of RNA detection effectively increased the detection of gene fusions. Our results provided the evidence for the precise treatment of bone tumors in the future.