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

Outani, Hidetatsu; Ikegami, Masachika; Imura, Yoshinori; Nakai, Sho; Takami, Haruna; Kotani, Yuki; Inoue, Akitomo; Okada, Seiji

doi:https://doi.org/10.1007/s10147-024-02673-2

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

Outani, Hidetatsu; Ikegami, Masachika; Imura, Yoshinori et al.

International Journal of Clinical Oncology, 2025, 30, 397-406

アクセス数:1,005件（2025-07-19 21:37 集計）

固定URL: https://hdl.handle.net/11094/100316

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タイトル	Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses
著者	NRID 1000060727965 1000060727965 researchmap permalink h-otani h-otani Scopus Author ID 6506224785 6506224785 著者名 Outani, Hidetatsu
	NRID 1000090830521 1000090830521 著者名 Ikegami, Masachika
	NRID 1000040772687 1000040772687 ORCID 0000-0002-0430-5894 0000-0002-0430-5894 researchmap permalink yoshinori.imura yoshinori.imura Scopus Author ID 55807487700 55807487700 著者名 Imura, Yoshinori
	NRID 1000000930207 1000000930207 researchmap permalink nakaisho nakaisho Scopus Author ID 57194235635 57194235635 著者名 Nakai, Sho
	著者名 Takami, Haruna
	著者名 Kotani, Yuki
	著者名 Inoue, Akitomo
	NRID 1000030448435 1000030448435 ORCID 0000-0002-5107-8209 0000-0002-5107-8209 researchmap permalink okadaseiji okadaseiji Scopus Author ID 35079139100 35079139100 著者名 Okada, Seiji
キーワード等	Cancer genome profiling
	Chemotherapy
	Chemotherapy sensitivity
	Gene alteration
	Osteosarcoma
内容	The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02673-2.
抄録	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.
出版者	Springer
収録物名	International Journal of Clinical Oncology
巻(号)	30
ページ	397-406
刊行年月	2025-02-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/100316
PISSN	13419625
eISSN	14377772
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1007/s10147-024-02673-2
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	International Journal of Clinical Oncology. 2025, 30, p. 397-406
DC.title	Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses
DC.creator	Outani, Hidetatsu
	Ikegami, Masachika
	Imura, Yoshinori
	Nakai, Sho
	Takami, Haruna
	Kotani, Yuki
	Inoue, Akitomo
	Okada, Seiji
DC.publisher	Springer
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-02-01
DC.identifier	https://doi.org/10.1007/s10147-024-02673-2
DC.subject	Cancer genome profiling
	Chemotherapy
	Chemotherapy sensitivity
	Gene alteration
	Osteosarcoma
DC.description	The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02673-2.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	100316
citation_title	Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses
citation_author	Outani, Hidetatsu
	Ikegami, Masachika
	Imura, Yoshinori
	Nakai, Sho
	Takami, Haruna
	Kotani, Yuki
	Inoue, Akitomo
	Okada, Seiji
citation_publisher	Springer
citation_language	英語
citation_date	2025-02-01
citation_journal_title	International Journal of Clinical Oncology
citation_volume	30
citation_firstpage	397
citation_lastpage	406
citation_doi	https://doi.org/10.1007/s10147-024-02673-2
citation_public_url	https://hdl.handle.net/11094/100316

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

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