Hairy Cell Leukemia: Morphological and Immunophenotypic Characteristics of Seven Cases and Cyclin D1 Expression

Aberrant immunophenotypic expression in hairy cell leukemia (HCL), both at medullary and extramedullary sites, is not uncommonly reported in literature. Cyclin D1 positivity in HCL may mimic mantle cell lymphoma (MCL) morphologically, especially in the presence of aberrant CD5 immunopositivity, requiring BRAFV600E mutation and/or CCND1 gene testing for confirmation. Here, we describe seven cases of HCL with clinicomorphological and immunophenotypic characteristics with an emphasis on cyclin D1 expression using immunohistochemistry (IHC) with a brief comprehensive literature review. We suggest that cyclin D1 positive HCL may be a distinct subtype which requires further immunophenotypic and molecular characterization for accurate diagnosis and planning of definitive therapy.

PD-L1 Expression Fluctuates Concurrently with Cyclin D in Glioblastoma Cells

Despite Glioblastoma (GBM) frequently expressing programmed cell death ligand-1 (PD-L1), treatment with anti-programmed cell death-1 (PD1) has not yielded brilliant results. Intratumor variability of PD-L1 can impact determination accuracy. A previous study on mouse embryonic fibroblasts (MEFs) reported a role for cyclin-D in control of PD-L1 expression. Because tumor-cell growth within a cancer is highly heterogeneous, we looked at whether PD-L1 and its cochaperone FKBP51s were influenced by cell proliferation, using U251 and SF767 GBM-cell-lines. PD-L1 was measured by Western blot, flow cytometry, confocal-microscopy, quantitative PCR (qPCR), CCND1 by qPCR, FKBP51s by Western blot and confocal-microscopy. Chromatin-Immunoprecipitation assay (xChIp) served to assess the DNA-binding of FKBP51 isoforms. In the course of cell culture, PD-L1 appeared to increase concomitantly to cyclin-D on G1/S transition, to decrease during exponential cell growth progressively. We calculated a correlation between CCND1 and PD-L1 gene expression levels. In the temporal window of PD-L1 and CCND1 peak, FKBP51s localized in ER. When cyclin-D declined, FKBP51s went nuclear. XChIp showed that FKBP51s binds CCND1 gene in a closed-chromatin configuration. Our finding suggests that the dynamism of PD-L1 expression in GBM follows cyclin-D fluctuation and raises the hypothesis that FKBP51s might participate in the events that govern cyclin-D oscillation.

The Influence of Gene Aberrations on Survival in Resected IDH Wildtype Glioblastoma Patients: A Single-Institution Study

This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

Cyclin D1 and p21 gene variants and oral squamous cell carcinoma risk and prognosis

Cyclin-dependent kinase inhibitor p21 (encoded by the CDKN1A gene) and cyclin D1 (encoded by the CCND1 gene) are important regulators of cell cycle progression and could have important effects in the complex process of neoplastic transformation. The current study aimed to investigate variants in CDKN1A (rs1801270, rs1059234) and CCND1 (rs9344) genes as potential risk and prognostic factors in oral squamous cell carcinoma (OSCC) patients. The study included 104 OSCC patients and 107 healthy individuals without a history of cancer. Genotypes were assessed by real-time PCR and TaqMan SNP genotyping. Significant differences in genotype distribution between OSCC cases and the control group were observed for the CCND1 rs9344 variant (p=0.017). According to the odds ratio (OR), adjusted for age and sex, the rs9344 heterozygous GA and homozygous mutated AA genotypes were associated with an increased OSCC susceptibility (OR=2.295, p=0.007; OR=2.029, p=0.037, respectively). Variants rs1801270 and rs105923 in CDKN1A were not associated with OSCC risk. There were no differences in overall survival among OSCC patients stratified by genotypes of the analyzed variants in CDKN1A and CCND1. Variant rs9344 in the CCND1 gene might be considered as a potential molecular risk factor for OSCC susceptibility but not for disease prognosis.

CYCLIN D1: As a Risk of Breast Cancer

Breast cancer is varying group of tumors in terms of disease prognosis. Breast cancer is found as second main cause of death related with cancer. Cyclin D1 (CCND1) is an important regulator of cell cycle. CCND1over expressed in various human cancers like head, oesophageal, neck, squamous, colon, breast, prostateetc. Many studies have conducted to find correlation between polymorphism in CCND1 gene and development of breast cancer. Some studies found certain genotypes related with risk of breast cancer development. Some studies also proposed the role of varying genetic backgrounds in breast cancer development. This review focuses on role of CCND1 polymorphism and possible risk factors associated with breast cancer, which may explicate the breast cancer screening, prevention, and treatments strategies for future use.

Correlation Between CCND1 Gene Polymorphism and Genetic Susceptibility to Gastric Cancer in Chinese Population

Objective: The relationship between Cyclin D1 gene (CCND1) rs9344 polymorphism and susceptibility to gastric cancer (GC) is investigated.Methods: In a case-control study, we selected 577 cases of GC from The People's Hospital Affiliated to Jiangsu University in China along with 678 normal controls. Blood DNA was extracted and PCR amplified, gene polymorphism was determined using Snapshot method.Results: Analysis reveals significant difference in smoking between GC and control groups (P=0.006), however, not on polymorphism (P＞0.05). Conclusion: Smoking is associated with gastric cancer, whereas CCND1 rs9344 polymorphism does not implicate susceptibility of gastric cancer.

HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma

Pyruvate kinase M2 (PKM2) is not only a key rate-limiting enzyme that guides glycolysis, but also acts as a non-metabolic protein in regulating gene transcription. In recent years, a series of studies have confirmed that post-translational modification has become an important mechanism for regulating the function of PKM2, which in turn affects tumorigenesis. In this study, we found that K62 residues were deacetylated, which is related to the prognosis of HCC. Further studies indicate that HDAC8 binds and deacetylates the K62 residue of PKM2. Mechanistically, K62 deacetylation facilitate PKM2 transport into the nucleus and bind β-catenin, thereby promoting CCND1 gene transcription and cell cycle progression. In addition, the deacetylation of K62 affects the enzyme activity of PKM2 and the flux of glucose metabolism. Therefore, these results suggest that HDAC8 / PKM2 signaling may become a new target for the treatment of HCC.