Outani Hidetatsu, Ikegami Masachika, Imura Yoshinori, Nakai Sho, Takami Haruna, Kotani Yuki, Inoue Akitomo, Okada Seiji
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, Japan.
Department of Musculoskeletal Oncology, Tokyo Metropolitan Cancer and Infection Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, Japan.
Int J Clin Oncol. 2025 Feb;30(2):397-406. doi: 10.1007/s10147-024-02673-2. Epub 2024 Dec 17.
Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response.
Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics.
The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age.
These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies.
骨肉瘤是最常见的原发性骨恶性肿瘤，具有复杂的遗传基础和两个发病高峰。对于年轻患者，标准治疗包括广泛手术切除联合辅助化疗；然而，化疗在老年患者中的作用仍存在争议。本研究的目的是调查年轻和老年骨肉瘤患者之间的遗传差异，并确定与化疗反应相关的基因特征。
使用从癌症基因组学和先进治疗中心获得的204例骨肉瘤患者的癌症基因组分析数据，分析基因改变情况。
突变谱与先前骨肉瘤的研究结果一致。CCNE1、MCL1、MYC和RB1改变与较年轻年龄显著相关，而CDK4、CDKN2A、CDKN2B、H3F3A、KMT2D、MDM2、RAC1和SETD2改变与较年长年龄显著相关。年龄、基因改变的无监督聚类以及MYC扩增与异环磷酰胺的反应显著相关。值得注意的是，聚类突变特征和MYC扩增均与年龄相关。
这些发现表明，不同的致癌机制导致年轻和老年患者对化疗的敏感性不同。癌症基因组分析可能有助于化疗选择，建议尽早实施以优化治疗策略。
