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

OBJECTIVE: To establish a method for detecting the exosomal PML-RARA fusion gene expression by droplet digital PCR (ddPCR). METHODS: By using Taqman probe-based ddPCR technique, the method that able to detect both long and short isoforms of PML-RARA fusion gene transcripts was established. RNA from PML-RARA negative cell line HL-60 as negative control was used to set the limit of blank (LOB), while the RNA from PML-RARA positive cell line NB4 and the recombinant plasmid pSG5-PML-RARA(S) were used to set the limit of detection (LOD) for long and short PML-RARA transcripts, respectively. Furtherly, the expression of exosomal PML-RARA fusion gene in NB4 cell culture supernatant and serum of patients with acute promyelocytic leukemia (APL) was analyzed by ddPCR technique. RESULTS: The LOB of ddPCR assay for long and short PML-RARA transcripts were 0.0725 and 0.083 copies per microliter of PCR reaction system, respectively, while the LOD of long and short PML-RARA transcripts were 0.19 and 0.21 copies per microliter of PCR reaction system, respectively. In addition, the expression of exosomal PML-RARA fusion gene derived from both NB4 cell culture supernatant and serum of APL patients was successfully detected. CONCLUSION A ddPCR-based technique for detecting fusion gene transcripts has been established, which can be used to analyze absolute quantification in the minimal quantity of PML-RARA transcripts derived from exosomes. It suggests the possibility of this technique to non-invasively and dynamicly monitore the exosomal PML-RARA transcripts from APL patients' serum.
Exosomes ; Gene Expression ; Humans ; Leukemia, Promyelocytic, Acute ; Oncogene Proteins, Fusion ; analysis ; Polymerase Chain Reaction ; Protein Isoforms

Humans ; Receptor, trkA/genetics* ; Neoplasms/genetics* ; Biomarkers, Tumor ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics*

Chromosome Aberrations ; Gene Fusion ; Genes, Tumor Suppressor ; Humans ; Oncogene Proteins, Fusion ; metabolism ; Oncogenes ; Pathology ; standards ; trends ; Soft Tissue Neoplasms ; genetics ; metabolism ; pathology

Adolescent ; Adult ; Female ; Fusion Proteins, bcr-abl ; genetics ; Gene Expression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Retrospective Studies

BACKGROUNDPrevious cytogenetic studies revealed aberrations varied among the three subtypes of rhabdomyosarcoma. We profiled chromosomal imbalances in the different subtypes and investigated the relationships between clinical parameters and genomic aberrations.

METHODSComparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging.

RESULTSChanges involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently (> 30%) seen in chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, 1q and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, 1p and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p, 6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p, 9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging.

CONCLUSIONSGains on chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.

Cell Line, Tumor ; Chromosome Aberrations ; Chromosomes, Human, Pair 12 ; genetics ; Comparative Genomic Hybridization ; methods ; Gene Fusion ; genetics ; Humans ; Oncogene Proteins, Fusion ; genetics ; Rhabdomyosarcoma ; genetics ; Tumor Cells, Cultured

Brain Neoplasms/surgery* ; Cyclic AMP Response Element-Binding Protein ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein EWS/genetics*

Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/pathology* ; Receptor Protein-Tyrosine Kinases/genetics* ; Gene Fusion ; Oncogene Proteins, Fusion/genetics*

Eosinophilia/genetics* ; Gene Rearrangement ; Humans ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Oncogene Proteins, Fusion/genetics* ; Receptor, Platelet-Derived Growth Factor alpha/genetics*