Anti-CCNE1 monoclonal antibody, clone FQS205

To obtain a better understanding of the genetic alterations of high-grade pancreatic intraepithelial neoplasia (HG-PanIN), we performed whole-genome copy number analysis by using single nucleotide polymorphism microarrays and targeted next-generation sequencing of 11 microdissected HG-PanIN and two low-grade PanIN lesions associated with HG-PanIN. HG-PanIN mutation profiles were compared with those of their associated invasive pancreatic ductal adenocarcinoma. All PanIN lesions harbored somatic KRAS mutations. The most common copy number Losses in the HG-PanIN were at the CDKN2A (9p21), TP53 (17p13), and SMAD4 (18q21) loci. Chromosomal losses in HG-PanIN were also found at 6p25-p24, 6q11-q27, 12q24, and 17q23-q24. Biallelic inactivation of CDKN2A and TP53 was detected in five of eight and in three of eight evaluable PanIN lesions, respectively. None of the HG-PanIN lesions had SMAD4 mutations or homozygous deletion. Copy number gains were noted at the MYC (8q24) and CCNE1 (19q12) loci and at 1q25-q31. Four HG-PanINs and one low-grade PanIN harbored chromothripsis-like regions. Five of seven pancreatic ductal adenocarcinomas evaluated had additional mutations that were not found in their associated HG-PanIN. HG-PanIN harbors widespread copy number alterations and commonly shows evidence of biallelic inactivation of CDKN2A and TP53 but not SMAD4. Chromothripsis events contribute to the copy number alterations of HG-PanIN.

Chromobox homolog 7 (CBX7) cooperates with other polycomb group (PcG) proteins to maintain target genes in a silenced state. However, the precise role of CBX7 in tumor progression is still controversial. We found that the expression of CBX7 in four public databases was significantly lower in high grade glioma (HGG). The reduced expression of CBX7 correlated with poor outcome in HGG patients. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway. We observed that decreased CBX7 protein levels enhanced glioma cells proliferation, migration and invasion. Then, we verified that CBX7 overexpression arrested cells in the G(0)/G(1) phase. Moreover, we demonstrated that the underlying mechanism involved in CBX7 induced repression of CCNE1 promoter requiring the recruitment of histone deacetylase 2 (HADC2). Finally, in vivo bioluminescence imaging and survival times of nude mice revealed that CBX7 behaved as a tumor suppressor in gliomas. In summary, our results validate the assumption that CBX7 is a tumor suppressor of gliomas. Moreover, CBX7 is a potential and novel prognostic biomarker in glioma patients. We also clarified that CBX7 silences CCNE1 via the combination of CCNE1 promoter and the recruitment of HDAC2.