STX11 functions as a novel tumor suppressor gene in peripheral T‐cell lymphomas. Issue 10 (13th August 2015)

• Record Type: Journal Article
• Authors: Yoshida, Noriaki; Tsuzuki, Shinobu; Karube, Kennosuke; Takahara, Taishi; Suguro, Miyuki; Miyoshi, Hiroaki; Nishikori, Momoko; Shimoyama, Masanori; Tsukasaki, Kunihiro; Ohshima, Koichi; Seto, Masao
• Is Part Of: Cancer science. Volume 106:Issue 10(2015:Oct.)
• Page Start: 1455
• Page End: 1462
• Publication Date: 2015-08-13
• Subjects: Functional analyses -- genomic loss of 6q24 -- peripheral T‐cell lymphomas -- STX11 -- tumor suppressor gene; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12742
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : STX11 acts as a tumor suppressor gene in T‐cell lymphomas. STX11 induction only suppressed the proliferation of T‐cell lines, which carried STX11 alterations. Other lineage cell lines such as NKL and Jeko1 cells allso carry a STX11 heterozygous loss, but they were not affected by STX11 induction.