Involvement of DPP9 in gene fusions in serous ovarian carcinoma.

Background: A fusion gene is a hybrid gene consisting of parts from two previously independent genes. Chromosomal rearrangements leading to gene breakage are frequent in high-grade serous ovarian carcinomas and have been reported as a common mechanism for inactivating tumor suppressor genes. However, no fusion genes have been repeatedly reported to be recurrent driver events in ovarian carcinogenesis.

Fusion genes with ALK as recurrent partner in ependymoma-like gliomas: a new brain tumor entity?

Background: We have previously characterized 19 ependymal tumors using Giemsa banding and high-resolution comparative genomic hybridization. The aim of this study was to analyze these tumors searching for fusion genes.

Methods: RNA sequencing was performed in 12 samples.

Sequential combination of karyotyping and RNA-sequencing in the search for cancer-specific fusion genes.

Cancer-specific fusion genes are often caused by cytogenetically visible chromosomal rearrangements such as translocations, inversions, deletions or insertions, they can be the targets of molecular therapy, they play a key role in the accurate diagnosis and classification of neoplasms, and they are of prognostic impact. The identification of novel fusion genes in various neoplasms therefore not only has obvious research importance, but is also potentially of major clinical significance. The "traditional" methodology to detect them began with cytogenetic analysis to find the chromosomal rearrangement, followed by utilization of fluorescence in situ hybridization techniques to find the probe which spans the chromosomal breakpoint, and finally molecular cloning to localize the breakpoint more precisely and identify the genes fused by the chromosomal rearrangement.

Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas.

The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. The first recurrent fusion transcript in serous ovarian carcinomas was reported by Salzman et al. in 2011, who used deep paired-end sequencing to detect the fusion gene ESRRA-C11orf20 in 10 out of 67 (15%) serous ovarian carcinomas examined, a finding that holds great promise for our understanding of ovarian tumorigenesis as well as, potentially, for new treatment strategies.

Fusion of ZMYND8 and RELA genes in acute erythroid leukemia.

Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap.

RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12).

Mesothelioma is a rare but very aggressive tumor derived from mesothelial cells. A number of often complex but nonrandom cytogenetic abnormalities have been found in these tumors, resulting in loss of chromosome bands 14q32 and 22q12 in more than 35% of the cases. In this study, we used RNA sequencing to search for fusion transcripts in a mesothelioma carrying a t(14;22)(q32;q12) as the sole chromosomal aberration and found an EWSR1-YY1 and its reciprocal YY1-EWSR1 fusion transcript.

Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X;22-translocation.

Endometrial stromal sarcomas (ESS) are genetically heterogeneous uterine tumors in which a JAZF1-SUZ12 chimeric gene resulting from the chromosomal translocation t(7;17)(p15;q21) as well as PHF1 rearrangements (in chromosomal band 6p21) with formation of JAZF1-PHF1, EPC1-PHF1, and MEAF6-PHF1 chimeras have been described. Here, we investigated two ESS characterized cytogenetically by the presence of a der(22)t(X;22)(p11;q13). Whole transcriptome sequencing one of the tumors identified a ZC3H7-BCOR chimeric transcript.

Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma.

Mesenchymal chondrosarcomas (MCs) account for 3-10% of primary chondrosarcomas. The cytogenetic literature includes only ten such tumours with karyotypic information and no specific aberrations have been identified. Using a purely molecular genetic approach a HEY1-NCOA2 fusion gene was recently detected in 10 of 15 investigated MCs.

A novel TCF3-HLF fusion transcript in acute lymphoblastic leukemia with a t(17;19)(q22;p13).

A 10-year-old boy was admitted to the hospital because of anemia detected after a two week history of fatigue, dizziness, nausea, headaches, and weight loss. A bone marrow investigation confirmed a diagnosis of acute lymphoblastic leukemia of the B-cell precursor phenotype. Chromosome G-banding analysis yielded the karyotype 46,XY,t(17;19)(q22;p13), and fluorescence in situ hybridization (FISH) analysis showed rearrangement of the genes TCF3 (on 19p13; accession number NM_03200 version 3) and HLF (on 17q22; accession number NM_002126 version 4) with the generation of a TCF3-HLF chimera.

Intestinal fatty acid binding protein (fabp2) in Atlantic salmon (Salmo salar): Localization and alteration of expression during development of diet induced enteritis.

In the present study full-length cDNAs corresponding to three isoforms of intestinal fatty acid binding protein (fabp2) in Atlantic salmon were cloned and characterized. Gene expression of fabp2 was observed in all tissues investigated, although differences were observed between isoforms. The highest fabp2a1, fabp2a2, and fabp2b expression was in the intestine.

Myelodysplastic syndrome with a t(2;11)(p21;q23-24) and translocation breakpoint close to miR-125b-1.

The upregulation of oncogenes and the formation of fusion genes are commonly observed in hematological malignancies with recurring balanced translocations. However, in some malignancies exhibiting balanced chromosomal rearrangements, neither oncogene deregulation nor generation of fusion genes appears to be involved, suggesting that other mechanisms are at play. In the rare myelodysplastic syndrome (MDS) containing a t(2;11)(p21;q23-24) translocation, breakpoints near a microRNA locus, miR-125b-1, in 11q24 have been suggested to be pathogenetically involved.

Novel fusion of MYST/Esa1-associated factor 6 and PHF1 in endometrial stromal sarcoma.

Rearrangement of chromosome band 6p21 is recurrent in endometrial stromal sarcoma (ESS) and targets the PHF1 gene. So far, PHF1 was found to be the 3' partner in the JAZF1-PHF1 and EPC1-PHF1 chimeras but since the 6p21 rearrangements involve also other chromosomal translocation partners, other PHF1-fusions seem likely. Here, we show that PHF1 is recombined with a novel fusion partner, MEAF6 from 1p34, in an ESS carrying a t(1;6)(p34;p21) translocation as the sole karyotypic anomaly.

Pigment-producing granulomatous myopathy in Atlantic salmon: a novel inflammatory response.

Melanin comprises a complex group of pigmented polymers whose primary function is ascribed to dermal solar protection, but may also have an interesting role in innate immunity. In ectothermic vertebrates, melanogenesis is reported in leukocyte populations, but it is not known if this occurs in connection with inflammatory reactions. Melanin accumulations in ectopic locations, in particular muscle, represent a serious quality problem in salmon production.

Identification of chromosomal breakpoints of cancer-specific translocations by rolling circle amplification and long-distance inverse PCR.

We describe the use of rolling circle amplification and long-distance inverse polymerase chain reaction (LD-PCR) to identify chromosomal breakpoints and fusion genes in cancer cells carrying acquired translocations. This approach produced enough template for 100 inverse PCR reaction from as little as 20 ng of patient DNA, consequently enabling the use of up to 500 times less patient DNA compared to standard inverse PCR. The method is based on identifying restriction sites in a putative breakpoint area in a cancer-specific translocation, followed by circularization and amplification of the restriction DNA products by using T4 DNA ligase and Phi29 enzyme, respectively.

The genome sequence of Atlantic cod reveals a unique immune system.

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes.

Identification of the TAF15-ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12).

We report the clinical, cytogenetic, and molecular data of two patients diagnosed with acute lymphoblastic leukemia characterized by the rare translocation t(12;17)(p13;q12). This translocation has been reported in 25 cases and its putative molecular consequence, the formation of a TAF15-ZNF384 fusion gene, in only six cases. We used fluorescence in situ hybridization followed by long-range polymerase chain reaction to find the translocation breakpoints.

Regulated expression of a transgene introduced on an oriP/EBNA-1 PAC shuttle vector into human cells.

Background: Sequencing of the human genome has led to most genes being available in BAC or PAC vectors. However, limited functional information has been assigned to most of these genes. Techniques for the manipulation and transfer of complete functional units on large DNA fragments into human cells are crucial for the analysis of complete genes in their natural genomic context.

Proteinase-activated receptor-2: two potential inflammatory mediators of the gastrointestinal tract in Atlantic salmon.

Proteinase-activated receptor 2 (PAR-2), activated by trypsin and other serine proteinases, is a key initiator of inflammatory responses in the intestine of mammals. Atlantic salmon fed diets with standard qualities of soybean meal (SBM) show enteritis of the distal intestine as well as increased activity of trypsin in both luminal contents and wall tissue. Luminal trypsin activity may possibly be involved in immune related disorders of the intestine also in Atlantic salmon via activation of PAR 2.

Characterization of a BAC library from channel catfish Ictalurus punctatus: indications of high levels of chromosomal reshuffling among teleost genomes.

The CHORI-212 bacterial artificial chromosome (BAC) library was constructed by cloning EcoRI/EcoRI partially digested DNA into the pTARBAC2.1 vector. The library has an average insert size of 161 kb, and provides 10.

A BAC-based physical map of the channel catfish genome.

Catfish is the major aquaculture species in the United States. To enhance its genome studies involving genetic linkage and comparative mapping, a bacterial artificial chromosome (BAC) contig-based physical map of the channel catfish (Ictalurus punctatus) genome was generated using four-color fluorescence-based fingerprints. Fingerprints of 34,580 BAC clones (5.

Isolation of the Atlantic salmon tyrosinase gene family reveals heterogenous transcripts in a leukocyte cell line.

In ectothermic vertebrates, visceral organs harbor melanin-containing cells. Their ability as pigment producers is nevertheless disputed. To address expression of the key genes for melanogenesis in Atlantic salmon (Salmo salar), a tyrosinase-positive leukocyte cell line (SHK-1) and skin were used to obtain full-length tyrosinase (Tyr), tyrosinase-like protein-1 (Tyrp1), and dopachrome tautomerase (Dct) mRNA transcripts.

Melanogenesis and evidence for melanosome transport to the plasma membrane in a CD83 teleost leukocyte cell line.

Visceral organs of ectothermic vertebrates harbour melanin-containing leukocytes termed melanomacrophages. These cells are thought to participate in immune reactions and free-radical trapping. In teleosts, the melanin-producing ability of melanomacrophages has hitherto not been confirmed by molecular techniques.

A physical map of the genome of Atlantic salmon, Salmo salar.

A physical map of the Atlantic salmon (Salmo salar) genome was generated based on HindIII fingerprints of a publicly available BAC (bacterial artificial chromosome) library constructed from DNA isolated from a Norwegian male. Approximately 11.5 haploid genome equivalents (185,938 clones) were successfully fingerprinted.

A highly redundant BAC library of Atlantic salmon (Salmo salar): an important tool for salmon projects.

Background: As farming of Atlantic salmon is growing as an aquaculture enterprise, the need to identify the genomic mechanisms for specific traits is becoming more important in breeding and management of the animal. Traits of importance might be related to growth, disease resistance, food conversion efficiency, color or taste. To identify genomic regions responsible for specific traits, genomic large insert libraries have previously proven to be of crucial importance.