2024-03-28T19:48:55Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02019652
2023-08-03T05:38:02Z
1642838163960:1642838338003
1642838403551:1642838407795
Molecular Signature of Tumors with Monoallelic 13q14 Deletion: a Case Series of Spindle Cell Lipoma and Genetically-Related Tumors Demonstrating a Link Between FOXO1 Status and p38 MAPK Pathway
Uehara, Karina
Ikehara, Fukino
Shibuya, Ryo
Nakazato, Iwao
Oshiro, Mariko
Kiyuna, Masaya
Tanabe, Yasuka
Toyoda, Zensei
Kurima, Kiyoto
Kina, Shinichiro
Hisaoka, Masanori
Kinjo, Takao
open access
© The Author(s) 2017
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Monoallelic 13q14 deletion
RB 1
FOXO 1
Reactive oxygen species
p38 MAPK
Spindle cell/pleomorphic lipomas (SCLs), cellular angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rare benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher β-catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis.
Frontiers Media
2018-10
eng
journal article
VoR
http://hdl.handle.net/20.500.12000/0002019652
https://u-ryukyu.repo.nii.ac.jp/records/2019652
https://doi.org/10.1007/s12253-017-0303-6
1219-4956
1532-2807
Pathology and Oncology Research (POR)
24
4
861
869
https://u-ryukyu.repo.nii.ac.jp/record/2019652/files/12253_2017_Article_303.pdf
5.7 MB