Open AccessSTX 11 functions as a novel tumor suppressor gene in peripheral T‐cell lymphomas
Author(s) -
Yoshida Noriaki,
Tsuzuki Shinobu,
Karube Kennosuke,
Takahara Taishi,
Suguro Miyuki,
Miyoshi Hiroaki,
Nishikori Momoko,
Shimoyama Masanori,
Tsukasaki Kunihiro,
Ohshima Koichi,
Seto Masao
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12742
Subject(s) - biology , pathogenesis , locus (genetics) , lymphoma , mutant , gene , suppressor , cell culture , peripheral t cell lymphoma , t cell , genetics , cancer research , microbiology and biotechnology , immunology , immune system
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, STX 11 and UTRN . The expression of STX 11, but not UTRN , was substantially lower in PTCL than in normal T‐cells. STX 11 sequence analysis revealed mutations in two cases (one clinical sample and one T‐cell line). We further analyzed the function of STX 11 in 14 cell lines belonging to different lineages. STX 11 expression only suppressed the proliferation of T‐cell lines bearing genomic alterations at the STX 11 locus. Interestingly, expression of a novel STX 11 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, STX 11 ‐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 STX 11 alteration. These results suggest that STX 11 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 .