Comprehensive phenotypic and genomic characterization of venous malformations

Hirose, Katsutoshi; Hori, Yumiko; Ozeki, Michio; Motooka, Daisuke; Hata, Kenji; Tahara, Shinichiro; Matsui, Takahiro; Kohara, Masaharu; Maruyama, Kazuaki; Imanaka-Yoshida, Kyoko; Toyosawa, Satoru; Morii, Eiichi

doi:https://doi.org/10.1016/j.humpath.2024.02.004

Comprehensive phenotypic and genomic characterization of venous malformations

Hirose, Katsutoshi; Hori, Yumiko; Ozeki, Michio et al.

Human Pathology, 2024, 145, 48-55

アクセス数:50件（2025-03-18 14:02 集計）

固定URL: https://hdl.handle.net/11094/94888

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タイトル	Comprehensive phenotypic and genomic characterization of venous malformations
著者	NRID 1000000824898 1000000824898 researchmap permalink -hirose -hirose Scopus Author ID 57190276392 57190276392 著者名 Hirose, Katsutoshi
	NRID 1000060528785 1000060528785 researchmap permalink yhhori yhhori 著者名 Hori, Yumiko
	NRID 1000060444303 1000060444303 著者名 Ozeki, Michio
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 著者名 Motooka, Daisuke
	NRID 1000080444496 1000080444496 researchmap permalink read0107167 read0107167 Scopus Author ID 8952419300 8952419300 ORCID 0000-0003-4367-9343 0000-0003-4367-9343 著者名 Hata, Kenji
	NRID 1000020792584 1000020792584 ORCID 0000-0001-6134-3275 0000-0001-6134-3275 researchmap permalink s_tahara s_tahara Scopus Author ID 57189030096 57189030096 著者名 Tahara, Shinichiro
	NRID 1000050747037 1000050747037 ORCID 0000-0002-6753-1688 0000-0002-6753-1688 researchmap permalink takahiromatsui takahiromatsui Scopus Author ID 35176152500 35176152500 著者名 Matsui, Takahiro
	ORCID 0009-0006-7636-5833 0009-0006-7636-5833 著者名 Kohara, Masaharu
	NRID 1000090821984 1000090821984 著者名 Maruyama, Kazuaki
	NRID 1000000242967 1000000242967 著者名 Imanaka-Yoshida, Kyoko
	NRID 1000030243249 1000030243249 ORCID 0000-0002-0338-0251 0000-0002-0338-0251 researchmap permalink osteobone0729 osteobone0729 Scopus Author ID 7003411866 7003411866 著者名 Toyosawa, Satoru
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 著者名 Morii, Eiichi
キーワード等	mTOR
	PIK3CA
	Sirolimus
	Spatial transcriptomics
	TEK
	Venous malformation
内容	Hirose K., Hori Y., Ozeki M., et al. Comprehensive phenotypic and genomic characterization of venous malformations. Human Pathology 145, 48 (2024); https://doi.org/10.1016/j.humpath.2024.02.004.
抄録	Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11.4%), and 2 (1.75%) patients, respectively. TEK-mutant VMs more commonly occurred in younger patients than TEK and PIK3CA mutation-negative VMs (other-mutant VMs), and showed more frequent skin involvement and no lymphocytic aggregates. No significant differences were observed in sex, location of occurrence, malformed vessel size, vessel density, or thickness of the vascular smooth muscle among the VM genotypes. Immunohistochemical analysis revealed that the expression levels of phosphorylated AKT (p-AKT) were higher in the TEK-mutant VMs than those in PIK3CA-mutant and other-mutant VMs. The expression levels of p-mTOR and its downstream effectors were higher in all the VM genotypes than those in normal vessels. Spatial transcriptomics revealed that the genes involved in “blood vessel development”, “positive regulation of cell migration”, and “extracellular matrix organization” were up-regulated in a TEK-mutant VM. Significant genotype-phenotype correlations in clinical and pathological features were observed among the VM genotypes, indicating gene-specific effects. Detailed analysis of gene-specific effects in VMs may offer insights into the underlying molecular pathways and implications for targeted therapies.
出版者	Elsevier B.V.
収録物名	Human Pathology
巻(号)	145
ページ	48-55
刊行年月	2024-03-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/94888
PISSN	00468177
eISSN	15328392
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.humpath.2024.02.004
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 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
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Human Pathology. 2024, 145, p. 48-55
DC.title	Comprehensive phenotypic and genomic characterization of venous malformations
DC.creator	Hirose, Katsutoshi
	Hori, Yumiko
	Ozeki, Michio
	Motooka, Daisuke
	Hata, Kenji
	Tahara, Shinichiro
	Matsui, Takahiro
	Kohara, Masaharu
	Maruyama, Kazuaki
	Imanaka-Yoshida, Kyoko
	Toyosawa, Satoru
	Morii, Eiichi
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-03-01
DC.identifier	https://doi.org/10.1016/j.humpath.2024.02.004
DC.subject	mTOR
	PIK3CA
	Sirolimus
	Spatial transcriptomics
	TEK
	Venous malformation
DC.description	Hirose K., Hori Y., Ozeki M., et al. Comprehensive phenotypic and genomic characterization of venous malformations. Human Pathology 145, 48 (2024); https://doi.org/10.1016/j.humpath.2024.02.004.
DCTERMS.abstract	Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11.4%), and 2 (1.75%) patients, respectively. TEK-mutant VMs more commonly occurred in younger patients than TEK and PIK3CA mutation-negative VMs (other-mutant VMs), and showed more frequent skin involvement and no lymphocytic aggregates. No significant differences were observed in sex, location of occurrence, malformed vessel size, vessel density, or thickness of the vascular smooth muscle among the VM genotypes. Immunohistochemical analysis revealed that the expression levels of phosphorylated AKT (p-AKT) were higher in the TEK-mutant VMs than those in PIK3CA-mutant and other-mutant VMs. The expression levels of p-mTOR and its downstream effectors were higher in all the VM genotypes than those in normal vessels. Spatial transcriptomics revealed that the genes involved in “blood vessel development”, “positive regulation of cell migration”, and “extracellular matrix organization” were up-regulated in a TEK-mutant VM. Significant genotype-phenotype correlations in clinical and pathological features were observed among the VM genotypes, indicating gene-specific effects. Detailed analysis of gene-specific effects in VMs may offer insights into the underlying molecular pathways and implications for targeted therapies.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	94888
citation_title	Comprehensive phenotypic and genomic characterization of venous malformations
citation_author	Hirose, Katsutoshi
	Hori, Yumiko
	Ozeki, Michio
	Motooka, Daisuke
	Hata, Kenji
	Tahara, Shinichiro
	Matsui, Takahiro
	Kohara, Masaharu
	Maruyama, Kazuaki
	Imanaka-Yoshida, Kyoko
	Toyosawa, Satoru
	Morii, Eiichi
citation_publisher	Elsevier B.V.
citation_language	英語
citation_date	2024-03-01
citation_journal_title	Human Pathology
citation_volume	145
citation_firstpage	48
citation_lastpage	55
citation_doi	https://doi.org/10.1016/j.humpath.2024.02.004
citation_public_url	https://hdl.handle.net/11094/94888

Comprehensive phenotypic and genomic characterization of venous malformations

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