Human HACE1 (E3 ubiquitin-protein ligase HACE1) ELISA Kit

HACE1 is an E3 ubiquitin ligase located in 6q21, the genomic region frequently deleted in natural killer (NK) cell malignancies. Here, we report HACE1 as a candidate tumor suppressor gene silenced through a combination of deletion and cytosine phosphate guanine island hypermethylation. We detected deletion of HACE1 in malignant NK cell lines (6 of 9, 67%) and primary biopsies (5 of 15, 33%) by quantitative PCR, with most of the specimen showing cytosine phosphate guanine island hypermethylation in the remaining allele, Leading to Low mRNA transcription. The ectopic expression of HACE1 in an HACE1-null NK cell Line led to apoptosis and G(2)/M cell cycle arrest. Moreover, HACE1 expression was up-regulated in IL-2-activated normal NK cells and NK cells cocultured with an engineered NK cell target, K562 Clone 9.mbIL21, suggesting its rote in the regulation of NK cell homeostasis. In conclusion, HACE1 is another potent tumor suppressor gene located within the 6q21 region, and loss of function of multiple tumor suppressor genes within 6q21 may be a critical determinant of NK cell Lymphomagenesis. (Am J Pathol 2013, 182: 49-55; http://dx.doi.org/10.1016/j.ajpath.2012.09.012)

To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without + 12, 11q-, 16q-, or HACE1 loss. RFS was better for those with than those without+ 12 (P =.010) and worse for those with than those without 11q-, 16q-, or HACE1 loss (P =.001, .025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and + 12 subgroup; high risk for the no + 12 plus 11q-, 16q-, or HACE1 loss subgroup; intermediate risk for the WT1 type and no + 12 plus no 11q-, 16q-, or HACE1 loss subgroup. Among the 27WTsexamined, the expression of 146 genes on chromosome 12was stronger in+ 12tumors than in no+ 12 tumors, while that of 10 genes on 16q wasweaker in 16q-tumors than in no 16q-tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. + 12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalitiesmay be related to altered gene expression associated with these abnormalities.