Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses.

IF 2.4 3区 医学 Q3 ONCOLOGY
Hidetatsu Outani, Masachika Ikegami, Yoshinori Imura, Sho Nakai, Haruna Takami, Yuki Kotani, Akitomo Inoue, Seiji Okada
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引用次数: 0

Abstract

Background: 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.

Methods: Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics.

Results: 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.

Conclusions: 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.

背景: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和辅助化疗;然而,化疗在老年患者中的作用仍存在争议。本研究旨在调查年轻和老年骨肉瘤患者的基因差异,并确定与化疗反应相关的基因特征:方法:利用癌症基因组学和高级治疗中心(Center for Cancer Genomics and Advanced Therapeutics)获得的204名骨肉瘤患者的癌症基因组图谱数据分析基因改变:结果:突变谱与以往骨肉瘤的研究结果一致。CCNE1、MCL1、MYC和RB1基因突变与年龄较小显著相关,而CDK4、CDKN2A、CDKN2B、H3F3A、KMT2D、MDM2、RAC1和SETD2基因突变与年龄较大显著相关。年龄、基因改变的无监督聚类和MYC扩增与伊佛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:这些研究结果表明,不同的致癌机制导致了年轻患者和老年患者对化疗的不同敏感性。癌症基因组图谱分析可能有助于化疗选择,建议尽早实施以优化治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.80
自引率
3.00%
发文量
175
审稿时长
2 months
期刊介绍: The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.
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