OBJECTIVE: To carry out combined genetic analysis on two patients suspected for Burkitt lymphoma to facilitate their diagnosis and treatment. METHODS: G banded karyotyping and interphase and metaphase fluorescence in situ hybridization (FISH) were used to detect the specific sites of chromosomes by using separate and fusion probes. RESULTS: The separate probe showed no presence of MYC gene abnormality, while fusion probe confirmed the IGH::MYC translocation in the samples. Combined with the clinical features and pathological characteristics, the two patients were finally diagnosed with Burkitt lymphoma, which was confirmed by targeted capture next generation sequencing. CONCLUSION The separate probe for the MYC gene has some shortcomings and should be used together with dual fusion probe to improve the accuracy of diagnosis.
Humans ; Burkitt Lymphoma/pathology* ; In Situ Hybridization, Fluorescence ; Genes, myc ; Translocation, Genetic ; Karyotyping

Although the exact etiology of cutaneous angiosarcoma remains unclear, MYC gene amplification has been recently discovered as a new pathogenesis. MYC is a proto-oncogene, and aberration of MYC signaling in malignancies is associated with tumor metastasis, recurrence, and mortality. Moreover, upregulation of the miRNA polycistron, miR-17-92 cluster, were confirmed in both cutaneous angiosarcoma and multiple myeloma with MYC amplification. The correlation between MYC and miRNA expression is predictable as the coincident aberrant phenotype in two diseases. Moreover, the exploiting MYC dependency may be an attractive disease-specific strategy for the diagnosis and treatment of patients who are unaware of the causes of cutaneous angiosarcoma. Herein, a rare case of cutaneous angiosarcoma of the foot, which is also the first case of cutaneous angiosarcoma accompanied by multiple myeloma, has been described.
Diagnosis ; Foot ; Genes, myc ; Hemangiosarcoma ; Humans ; MicroRNAs ; Mortality ; Multiple Myeloma ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogenes ; Recurrence ; Up-Regulation

OBJECTIVETo analyze the clinicopathological features and prognostic factors of patients with diffuse large B-cell lymphoma(DLBCL).

METHODSNinety-four cases of DLBCL followed up were selected in Fujian Tumor Hospital. The immunohistochemistry method was used to detect the protein expressions of BCL-2 BCL-6, MYC, CD10 and MUM-1, the gene abnormalities of MYC and BCL-2 were analyzed by fluorescence in situ hybridization, and the clinical pathological features and the related factors affecting prognosis in the patients with DLBCL were analyzed.

RESULTSThe protein positive rates of BCL-2, BCL-6, MYC, CD10 and MUM-1 in 94 patients were 75.53% (71/94), 58.51% (55/94), 52.13% (49/94), 15.96% (15/94) and 34.04% (32/94) respectively. The detection rate of MYC gene abnormality was 20.93% (9/43) and the detection rate of BCL-2 gene abnormality was 44% (22/50); 2 kinds of gene abnormalities were of multiple copies, and 2 cases (2.13%) were abnormal in MYC and BCL-2 genes simultaneously. The median survival time of 3 years in 94 patients was 21.79 months (2-36 months), and the overall survival rates of 1 and 3 years were 82.98% and 64.89% respectively. Single factor analysis revealed that the high ECOG score (≥ 2), high international prognostic index (IPI) classification, positive expression of BCL-6 protein, and MYC and BCL-2 gene simultaneously abnormal were the risk factors influencing the prognosis (all P<0.05). COX regression analysis showed that IPI classification, ECOG score and treatment methods were independent factors influencing the prognosis (all P<0.05).

CONCLUSIONIPI classification, ECOG score and treatment methods have greater impacts on the prognosis of patients with DLBCL. Chemotherapy combined with radiotherapy or surgical treatment can significantly improve the prognosis of patients.

Genes, myc ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-bcl-6

OBJECTIVETo explore the effect of decitabine on Dickkopf-1 (DKK1) gene expression level and its downstream Wnt signaling pathway in acute myeloid leukemia (AML) cell line HL-60.

METHODSFlow cytometry and DNA ladder analysis were performed to detect apoptosis in HL-60 cell treated with different concentration of decitabine. Methylation-specific polymerase chain reaction (MS-PCR) was used to examine the methylation status of DKK1 gene. The expressions of mRNA and protein were determined by qRT-PCR and Western blot, respectively.

RESULTSFlow cytometric detection showed that after treating HL-60 cell line with decitabine of different concentrations for 48 h, the early apoptosis of HL-60 cells increased significantly as compared with control group (P < 0.05). DNA ladder analysis showed that the DNA ladder and demethylation of DKK1 gene appeared. RT-PCR and Western blot showed that the expressions of mRNA and protein increased. The protein expressions of β-catenin and C-MYC decreased.

CONCLUSIONThe decitabine can promote the apoptosis of HL-60 cells throngh demethylation of DDK1 gene and inhibition of Wnt signalling pathway.

Apoptosis ; Azacitidine ; analogs & derivatives ; pharmacology ; DNA Methylation ; Gene Expression Regulation, Bacterial ; Genes, myc ; HL-60 Cells ; drug effects ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Leukemia, Myeloid, Acute ; pathology ; RNA, Messenger ; Wnt Signaling Pathway ; beta Catenin ; metabolism

Multiple myeloma(MM) as one of the most common tumors of hmatologic system, is characterized by malignant proliferation of plasma cells, and the chemotherapy is the main therapeutic method. MM is an incurable disease because of drug-resistance of MM cells. Although the pathogenesis of MM remains unknown, the chromosome abnormalities exit in half of the patients, particularly the highly expressed gene C-MYC. Furthermore, plenty of clinical researches indicated a high expression level of C-MYC implied worse progression and/or poor prognosis of MM. Recently, the work exploiting the compounds targeting MYC has made substantial progress, even in the MM therapy. In this article, briefly the recent advances of the research on C-MYC proto-oncogene in multiple myeloma are reviewed.
Chromosome Aberrations ; Genes, myc ; Humans ; Multiple Myeloma ; Plasma Cells ; Proto-Oncogene Proteins c-myc

OBJECTIVETo investigate the effect and possible mechanism of bromo-domain inhibitors (JQ1) on proliferation inhibition and inducing apoptosis of acute T lymphocyte leukemia cell line (Jurkat) .

METHODSJurkat cell line was treated by JQ1 at different concentrations. MTT was used to detect the cell proliferation inhibition rate. The flow cytometry with AnnexinV-FITC/PI fluorescence staining was used to detect the changes of apoptosis rate, and real-time fluorescent quantitative PCR was used to detect c-Myc/Notch1 gene expression levels.

RESULTSWith the increasing of drug concentration and prolonging of time, the inhibitory rate of Jurkat cell growth was enhanced in time-dose dependent manner; Jurkat cells was treated by 0.8, 1.6, and 4 µ mol/LJQ1 for 48 h and 72 h, the cell apoptosis rate was enhanced with the increase of drug concentration and prolonging of time, and the difference was statistically different in comparison with the control group(P<0.05); PCR detection indicated that Notch1 and c-Myc mRNA expression was reduced in 48 h after JQ1 treatment, which was statistically different from the control group,(P<0.05) .

CONCLUSIONJQ1 can effectively inhibit the growth of Jurkat cell line, and potentially induce apoptosis through Notch1 and c-Myc gene. Hence JQ1 may be one of new methods used to treat T-ALL.

Apoptosis ; Azepines ; Cell Proliferation ; Flow Cytometry ; Genes, myc ; Humans ; Jurkat Cells ; Nuclear Proteins ; Transcription Factors ; Triazoles

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

BACKGROUDF-Box and WD40 domain containing protein 7 gene (FBXW7) is part of the E3 ubiquitin ligase complex that controls the turnover of various proteins including NOTCH1, c-MYC and Cyclin E.

OBJECTIVETo investigate the mutations of FBXW7 gene in adult T-cell acute lymphoblastic leukemia (T-ALL).

METHODSExon 5-12 of FBXW7 were amplified, cloned and sequenced in 54 adult T-ALL patients; the frequency, position and types of FBXW7 mutation were analyzed; the co-existing of mutations with NOTCH1 and their relevant prognostic significance were explored as well.

RESULTSFBXW7 mutations were identified in 11.1% of adult T-ALL patients. A total of 4 types of point mutations (R465H, R465L, R479P and R505C) and 1 deletion/insertion mutation were observed, and all of them located in WD40 domain of FBXW7. In addition, co-existing mutations with NOTCH1 were identified in 83.3% of patients with FBXW7 mutation. Notably, the co-existed NOTCH1 mutations, including 3 point mutations (L1574P, L1596H and L1600P) and 2 deletion/insertion mutations located in HD domain. Furthermore, patients with FBXW7 mutation only had significantly longer overall survival compared with those without mutation (P=0.049).

CONCLUSIONFBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.

Adult ; Cell Cycle Proteins ; Exons ; F-Box Proteins ; F-Box-WD Repeat-Containing Protein 7 ; Genes, myc ; Humans ; Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Ubiquitin-Protein Ligases

OBJECTIVETo study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in reversing multidrug resistance in vincristine-resistant human gastric cancer SGC7901/VCR cells.

METHODSMTT assay was used to measure the 50% inhibiting concentration (IC₅₀) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments. SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT-PCR, RT-qPCR and Western-blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c-myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c-myc were determined by RT-PCR and Western-blot analysis.

RESULTSAfter combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC₅₀ of VCR, DDP, ADM, and 5-Fu treatment was significantly decreased compared with the control group or TRAIL-treated group (P < 0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0.4 µg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down-regulation of DNA-PKcs/Akt/GSK-3β signaling pathway, and higher inhibition of MDR1(P-gp) and MRP1 than those treated with TRAIL alone (P < 0.01 for all). The mRNA and protein levels of DR4, DR5, c-myc were significantly decreased after silencing c-myc with specific siRNA in the SGC7901/VCR cells (P < 0.01 for all), and were significantly increased after transfection of recombinant plasmid c-myc into the SGC7901/VCR cells (P < 0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0.25 µg/ml DDP + 10 ng/ml TRAIL and 0.5 µg/ml DDP + 10 ng/ml TRAIL, the relative expression level of c-myc protein in the SGC7901/VCR cells was 0.314 ± 0.012, 0.735 ± 0.026, and 0.876 ± 0.028, respectively, and the relative expression of cytochrome C was 0.339 ± 0.036, 0.593 ± 0.020 and 0.735 ± 0.031, respectively, and the relative expression levels of DR4, DR5, active-caspase 3 and active-caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations.

CONCLUSIONSThe activation of DNA-PKcs/Akt/GSK-3β signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi-drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up-regulating c-myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP-induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; administration & dosage ; pharmacology ; Formazans ; Genes, myc ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Inhibitory Concentration 50 ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Plasmids ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Stomach Neoplasms ; drug therapy ; pathology ; TNF-Related Apoptosis-Inducing Ligand ; administration & dosage ; pharmacology ; Tetrazolium Salts ; Transfection ; methods

OBJECTIVETo investigate the effect of BCL-2/MYC double-hit on prognosis in diffuse large B-cell lymphoma（DLBCL）.

METHODSA retrospective study was conducted to investigate clinical and pathological data of 111 patients with DLBCL. CD10, BCL-6, MUM-1, BCL-2 protein expressions were examined by immune-histochemical methods, and abnormal BCL-2 and MYC genes were analyzed by FISH for patients with sufficient pathological data. SAS 8.2 was adopted to perform Chi- square test, COX's proportional Hazard Model, Life table survival analyses.

RESULTSOf 111 patients, male 77 cases, female 34 cases, the median age was 55（14-85）years, CD10, BCL-6, MUM-1, BCL-2 positive rates were 15.7%（16/102）, 58.8%（60/102）, 33.0%（34/103）, 74.8（77/103）respectively, the abnormal rate of BCL-2 gene was 43.1%（25/58, 24 cases with multiple copies, 1 case with translocation）, and the abnormal rate of MYC gene was 20.4%（10/49, 10 cases with multiple copies）. Coexistence of BCL-2 and MYC genes abnormalities accounted for 13.0%（6/46）. According to the classification of Hans model, GCB subgroup accounted for 41.2%（42/102）, and non-GCB subgroup 58.8%（60/102）, the median survival time was 24 months, 3-year and 5-year overall survival rates were 48.5% and 39.7% respectively. Overall survival rates of normal and abnormal BCL-2 gene were 34.2%，22.8%, respectively with no statistical significance（P=0.770）. Overall survival rates of normal and abnormal MYC gene were 35.9% and 22.2% ，with no statistical significance（P=0.650）. Overall survival rate of double-hit was 0, far worse than that of single abnormal gene（P=0.034）, which implied double-hit of BCL-2 and MYC gene abnormality to be adverse prognostic factors. BCL-6 protein express could be classified as benign prognostic factors, while ECOG score≥2, escalated IPI index as adverse prognostic factors, and further COX risk model regression analysis indicated that ECOG score, IPI grading and treatment methods were independently adverse factors affecting prognosis. Comprehensive therapy based on chemotherapy could improve outcome.

CONCLUSIONBCL-2/MYC genes double-hit was the factor for the adverse outcome in DLBCL patients. However, ECOG score, IPI risk grading and treatment methods were the independent factors affecting prognosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Genes, myc ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; Retrospective Studies ; Survival Rate ; Translocation, Genetic ; Young Adult