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Title: STX11 functions as a novel tumor suppressor gene in peripheral T-cell lymphomas
Authors: Yoshida, Noriaki
Tsuzuki, Shinobu
Karube, Kennosuke
Takahara, Taishi
Suguro, Miyuki
Miyoshi, Hiroaki
Nishikori, Momoko  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-4171-2162 (unconfirmed)
Shimoyama, Masanori
Tsukasaki, Kunihiro
Ohshima, Koichi
Seto, Masao
Author's alias: 錦織, 桃子
Keywords: Functional analyses
Genomic loss of 6q24
Peripheral T-cell lymphomas
STX11
Tumor suppressor gene
Issue Date: Oct-2015
Publisher: Wiley Publishing Asia Pty Ltd.
Journal title: Cancer Science
Volume: 106
Issue: 10
Start page: 1455
End page: 1462
Abstract: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Their molecular pathogenesis has not been entirely elucidated. We previously showed that 6q24 is one of the most frequently deleted regions in primary thyroid T-cell lymphoma. In this study, we extended the analysis to other subtypes of PTCL and performed functional assays to identify the causative genes of PTCL that are located on 6q24. Genomic loss of 6q24 was observed in 14 of 232 (6%) PTCL cases. The genomic loss regions identified at 6q24 always involved only two known genes, STX11 and UTRN. The expression of STX11, but not UTRN, was substantially lower in PTCL than in normal T-cells. STX11 sequence analysis revealed mutations in two cases (one clinical sample and one T-cell line). We further analyzed the function of STX11 in 14 cell lines belonging to different lineages. STX11 expression only suppressed the proliferation of T-cell lines bearing genomic alterations at the STX11 locus. Interestingly, expression of a novel STX11 mutant (p.Arg78Cys) did not exert suppressive effects on the induced cell lines, suggesting that this mutant is a loss-of-function mutation. In addition, STX11-altered PTCL not otherwise specified cases were characterized by the presence of hemophagocytic syndrome (67% vs 8%, P = 0.04). They also tended to have a poor prognosis compared with those without STX11 alteration. These results suggest that STX11 plays an important role in the pathogenesis of PTCL and they may contribute to the future development of new drugs for the treatment of PTCL.
Rights: © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
URI: http://hdl.handle.net/2433/215154
DOI(Published Version): 10.1111/cas.12742
Appears in Collections:Journal Articles

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