Carcinoma, Adenoid Cystic ; genetics ; Humans ; Oncogene Proteins, Fusion ; genetics

Humans ; Sarcoma ; Transcription Factors ; Biomarkers, Tumor ; Oncogene Proteins, Fusion

OBJECTIVETo study the relationship between TMPRSS2: ERG gene fusion and the pathological grade of prostate cancer (PCa).

METHODSWe collected fresh prostatic tissue samples from 62 patients with PCa and another 10 with benign prostatic hyperplasia ( BPH) and included 9 cancer cell strains as the control. We examined the TMPRSS2:ERG fusion gene in the PCa samples by nest RT-PCR, compared the Gleason scores between the TMPRSS2:ERG-positive and -negative cases, and analyzed the association of TMPRSS2: ERG fusion with the pathological features of PCa.

RESULTSThe TMPRSS2: ERG fusion gene was detected in 28 (45.16%) of the PCa cases, but in none of the 10 BPH cases or the 9 cancer cell strains. No statistically significant differences were found in the Gleason scores between the TMPRSS2:ERG-positive and -negative cases (Z = -0.609, P = 0.542), but the primary Gleason score was markedly higher in the former than in the latter (Z = -2.600, P = 0.009). Univariate logistic regression analysis showed that TMPRSS2:ERG was associated with the cribriform growth pattern (OR = 6.250, P = 0.002), foamy gland morphology (OR = 6.666, P = 0.023), and signet-ring cells (OR = 3.240, P = 0.035), but multivariate logistic regression analysis manifested that it was associated with the cribriform growth pattern only (OR = 3.750, P = 0.033).

CONCLUSIONTMPRSS2:ERG gene fusion was associated with higher pathological grades of prostate cancer.

Gene Fusion ; Humans ; Male ; Oncogene Proteins, Fusion ; genetics ; Prostatic Hyperplasia ; genetics ; Prostatic Neoplasms ; genetics ; pathology

Humans ; Clinical Relevance ; Receptor, trkA/genetics* ; Neoplasms ; Digestive System Neoplasms/genetics* ; Oncogene Proteins, Fusion/genetics* ; Gene Fusion

Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
Aged ; China ; Humans ; Male ; Middle Aged ; Oncogene Fusion/genetics* ; Oncogene Proteins, Fusion/genetics* ; Prostatic Neoplasms/genetics* ; Serine Endopeptidases/genetics* ; Transcriptional Regulator ERG/genetics*

Humans ; Infant ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Brain Neoplasms/surgery* ; Glioma/surgery* ; Oncogene Proteins, Fusion/genetics* ; Lung Neoplasms

Female ; Humans ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Neoplasms, Muscle Tissue/genetics* ; Uterus ; Oncogene Proteins, Fusion/genetics* ; Lung Neoplasms ; Proteins

OBJECTIVEThis study was to establish a stable, effective and reproducible human acute promyelocytic leukemia model in severe combined immunodeficient (SCID) mice by using NB4 cell line, and to investigate the disease course character and biological behaviors.

METHODSThree-five-week-old SCID beige mice were divided randomly into two groups: experimental and control group. SCID mice of experimental group were transplanted by tail vein (iv) injection of 5×10(6) NB4 cells. The WBC cell count and the positive rate of promyelocytes in peripheral blood were dynamically monitored by using smears. Morphological examination and histopathological assay were employed to confirm NB4 cell infiltration in organs (liver, spleen, lung, kidney and brain). The expression level of PML-RARα fusion protein was detected by Western blot.

RESULTSWithin two weeks there was no significant difference in peripheral blood WBC count between two groups (P > 0.05), meanwhile, NB4 cells were not found. At the day 21 and 28 after inoculation, the peripheral blood white blood cell count of experimental group reached to (4.79 ± 1.13)×10(9)/L and (7.62 ± 2.24)×10(9)/L respectively, which were significantly higher than that in control group (P < 0.05); simultaneously, the positive rates of promyelocytes on smears were (2.14 ± 0.63)% and (6.6 ± 2.76)%, respectively. Morphological observation showed single or multiple tumor lumps at day 21 after inoculation; HE staining of tissue biopsies demonstrated a large number of promyelocyte in the liver, spleen, lung, kidney and brain tissue. Cell immunofluorescence results showed that the CD33 expression of bone marrow cells in mice of experimental group was strongly positive (P < 0.05). Western blot confirmed that the PML-RARα fusion protein was expressed variously in liver, kidney and brain tissue.

CONCLUSIONSThe human acute promyelocytic leukemia SCID mouse model is succesfully established by tail vein injection of NB4 cells. This model can mimic the characters of involved bone marrow and diffuse growth of cells. This model is a useful tool to explore the pathogenic mechanism and experimental treatment of human leukemia.

Animals ; Cell Line ; Granulocyte Precursor Cells ; Humans ; Leukemia, Promyelocytic, Acute ; Mice ; Mice, SCID ; Oncogene Proteins, Fusion

OBJECTIVETo investigate the first switched time of PML/RARα fusion gene in patients with acute promyelocytic leukemia (APL) and its clinical significance.

METHODSsixty cases of newly diagnosed APL were enrolled in this study. They received standard remission induction, consolidation and maintenance treatments according to the clinical pathway for APL, and were followed up. During the same time the PML/RARα fusion gene mRNA expression of all cases was detected by multi-nested PCR.

RESULTSexcept for 3 death cases and 1 case failed to follow-up, the PML/RARα fusion genes in the remaining 56 cases were firstly found to be negative from 24 to 381 days respectively, the mean value of the first switched time was 131 ± 90 days. There was no statistically significant difference in age, sex and risk stratification between different groups. However, the cases with L-type PML/RARα gene had shorter time compared with the patients with S-type PML/RARα gene (P = 0.032); then, for the above-mentimed 56 cases, the follow-up duration ranged from 25-1979 days (median 946 days), long-term molecular remissions had been observed in most cases, but 1 case with the first switched time of 133 days unfortunately recurred to be positive and followed by clinical relapse.

CONCLUSIONThe PML/RARα fusion gene in newly diagnosed APL patients was first switched to be negative in about 4 months after treatment. The first switched time of PML/RARα fusion gene can objectively reflect the reduction of leukemia cells, and the differences among different subtypes of PML/RARα fusion gene may have some suggestions for the treatment, but without important significance for the evaluation of prognosis and recurrence for APL patients. In addition, minimal residual disease (MRD) can be dynamically monitored by detecting PML/RARα fusion gene, thus having an important clinical significance for analysis of APL recurrence.

Humans ; Leukemia, Promyelocytic, Acute ; Neoplasm, Residual ; Oncogene Proteins, Fusion ; Polymerase Chain Reaction ; Prognosis ; Recurrence ; Remission Induction

OBJECTIVETo explore CBFbeta/MYH11 fusion transcripts and its expressing product CBFbeta/SMHHC fusion protein in mechanism of leukemogenesis.

METHODSCBFbeta/MYH11 fusion transcripts were detected by combined RT-PCR with sequencing. Transcription assays were examined using pM-CSFR-Luc as reporting plasmid, and subcellular localization of encoding proteins were assayed by double immunofluorescent staining and Western blot.

RESULTSTwo types of CBFbeta/MYH11 fusion transcripts were found in 26 patients with acute leukemia, most being of type A (23/26 cases, 92%) and a few of type D (2/26 cases, 8%). The inhibition of CBF-mediated M-CSFR promotor transactivation by CBFbeta/SMHHC fusion protein was increasing with the increase in amount of the fusion protein. CBFalpha subunit (AML1) located in nucleus, both CBFbeta subunit (CBFbeta) and CBFbeta/SMHHC located in cytoplasm. When AML1 and CBFbeta were coexpressed, CBFbeta still located mainly in cytoplasm, but when AML1 and CBFbeta/SMHHC were coexpressed, CBFbeta/SMHHC located mainly in nucleus.

CONCLUSIONS(1) The types of CBFbeta/MYH11 fusion transcripts of Chinese leukemia patients are almost the same as that reported in western literature. (2) CBFbeta/SMHHC inhibits CBF-mediated transactivation through competing with CBFbeta for binding to AML1.

Adult ; Female ; Humans ; Leukemia, Myelomonocytic, Acute ; genetics ; metabolism ; Male ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Transcription, Genetic