| 1. |
- Macchia, Gemma, et al.
(författare)
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Rearrangements of chromosome bands 15q12-q21 are secondary to HMGA2 deregulation in conventional lipoma.
- 2014
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 31:2, s. 807-811
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Tidskriftsartikel (refereegranskat)abstract
- Rearrangements of chromosome arm 15q are rare but recurrent in conventional lipomas, a tumor type often showing deregulated expression of the HMGA2 gene. In order to assess whether 15q rearrangements could constitute a distinct pathogenetic mechanism, we studied seven cases of conventional lipoma that at G-banding analysis had various rearrangements of 15q12-q21. The breakpoints in 15q were mapped by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array analyses, and the status of the HMGA2 gene was evaluated by FISH and/or quantitative PCR. We found an overlapping deletion on 15q in two cases, but no recurring breakpoint among the other cases. In addition, all cases displayed rearrangement of HMGA2 at the genomic or the transcriptional level. Although 15q rearrangements sometimes are noted as the sole aberration at cytogenetic analysis of conventional lipomas, they are secondary to HMGA2 deregulation.
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| 2. |
- Möller, Emely, et al.
(författare)
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Bidirectionality and transcriptional activity of the EWSR1 promoter region
- 2009
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 21:3, s. 641-648
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Tidskriftsartikel (refereegranskat)abstract
- EWSR1 is involved in chimeric proteins which play crucial roles in the development of a variety of bone and soft tissue tumors. Many of the chimeric genes involving EWSR1 have been extensively studied, whereas less is known about the wild-type (wt) gene and its regulation. As the expression of the chimeric gene is driven by the EWSR1 promoter, it is of importance to study the mechanisms regulating wt EWSR1 expression. We estimated the transcriptional activity of the EWSR1 promoter through deletion fragments driving reporter gene expression. This assay identified the 100-bp region immediately downstream of the EWSR1 transcriptional start site (+1) and the downstream region from +100 to +300 as important regions for transcriptional regulation. We also found that EWSR1 and RHBDD3, a gene located directly upstream of EWSR1 that is likely to share regulatory elements with EWSR1, were co-expressed in the tissue panels, Ewing tumor biopsies and cell lines. Thus, our results show that the EWSR1 promoter functions in a bidirectional manner, thereby regulating also RHBDD3, and identifies specific regions that strongly influence promoter activity.
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| 3. |
- Nilsson, Malin A, et al.
(författare)
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Atypical lipomatous tumor with rare structural rearrangements involving chromosomes 8 and 12
- 2005
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 13:4, s. 649-652
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Tidskriftsartikel (refereegranskat)abstract
- Atypical lipomatous tumor (ALT), an intermediate malignant neoplasm of soft tissues, is characterized by the presence of supernumerary ring and giant marker chromosomes. These supernumerary chromosomes consistently contain amplified 12q-material in association with amplified segments from a variety of other chromosomes. However, a few cases of ALT with other types of chromosomal rearrangements have been reported earlier. We report on new types of structural aberrations in a case of ALT. In a pseudodiploid karyotype, there were two aberrant chromosomes, both consisting of alternating chromosome 8 and 12 sequences as shown by multicolor fluorescence in situ hybridization (FISH). The complex rearrangement was not only the result of multiple breaks and reunions of these chromosomes, but was also associated with a gain of chromosome 12 sequences. FISH analyses revealed that the number of MDM2 signals was slightly elevated (median, 5). There were three intact copies of HMGA2 and one additional copy of the 5' part of the gene. These findings are consistent with previous reports that the ALT phenotype may be associated with a low or moderate level of gene amplification, whereas truncation of HMGA2 has been observed in both ALTs and benign lipomas. The aberrations in the present case were stable, although rare cells with higher MDM2 copy numbers were detected. Whether ALTs with these types of aberrations have a lower risk of tumor progression than ALTs with the notoriously mitotically unstable ring and giant marker chromosomes remains to be investigated.
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| 4. |
- Panagopoulos, Ioannis, et al.
(författare)
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Characterization of an alternative transcript of the human CREB3L2 gene.
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 24:5, s. 1133-1139
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Tidskriftsartikel (refereegranskat)abstract
- CREB3L2, a member of the CREB3 family of transcription factors, spans >120 kbp and is composed of 12 exons. We characterized a widely expressed transcript of CREB3L2 generated by an intronic polyadenylation site in intron 4 of the gene. It could be translated to a CREB3L2 variant which is localized both in the nucleus and the endoplasmatic reticulum. The protein retains the N-terminal transactivation domain but lacks the DNA-binding domain, the transmembrane domain and the C-terminal part. Experiments using a GAL4 DNA-binding domain fusion model showed that the transcript is a transactivator but it cannot exert its function through the CRE and ATF6 binding sites and has little effect on the GRP78 promoter. Whether this transcript has a cellular function or is targeted for degradation by nonsense-mediated RNA decay system of RNA surveillance is currently unknown.
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| 5. |
- Panagopoulos, Ioannis, et al.
(författare)
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Characterization of the human CREB3L2 gene promoter
- 2009
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 21:3, s. 615-624
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Tidskriftsartikel (refereegranskat)abstract
- CREB3L2 encodes a member of the CREB3 family of transcription factors. We characterized its promoter region, showing that it is asymmetrically bidirectional, also driving the expression of a variant of AKR1D1. It has a CRE binding site which is conserved among mammalians; removal or alteration of it resulted in reduced promoter activity. When transiently transfecting the HEK293 cell line with constructs with partially deleted promoter regions, 5' deletions beyond 1058-bp upstream of the transcription starting site resulted in successive reduction of the activity. The inclusion of the untranslated part of CREB3L2 exon 1 strongly inhibited the promoter activity. Forskolin resulted in a decreased reporter activity, whereas phorbol 12-myristate 13-acetate increased the promoter activity irrespective of the status of the CRE binding site. The presence of the CRE site indicates autoregulation of CREB3L2 and/or regulation via other members of the CREB3 family or a variety of bZIP transcription factors.
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| 6. |
- Panagopoulos, Ioannis, et al.
(författare)
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The POU5F1P1 pseudogene encodes a putative protein similar to POU5F1 isoform 1.
- 2008
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 20:5, s. 1029-1033
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Tidskriftsartikel (refereegranskat)abstract
- POU5F1, which encodes a transcriptional factor, has two alternatively spliced transcripts, 1 and 2, as well as six pseudogenes. Transcript 1 is considered to be a key regulator of cellular pluripotency and self-renewal. The POU5F1 pseudogene, POU5F1P1 on 8q24, encodes a protein with 95% homology with the isoform 1 of POU5F1. It is located 15 kbp downstream of the SNP rs6983267, which is strongly associated with an increased risk of prostate and colon cancer, and within the amplified region in a variety of human malignancies. The previous finding of expressed sequence tags suggests that POU5F1P1 can be expressed. We showed that a putative POU5F1P1 protein is localized in the nucleus, acts as a transcriptional activator and regulates the expression in a similar way to the POU5F1 isoform 1. However, POU5F1P1 was a weaker activator than isoform 1 of POU5F1, possibly due to the amino acid substitutions.
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| 7. |
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