| 1. |
- Barbouti, Aikaterini, et al.
(författare)
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Multicolor COBRA-FISH analysis of chronic myeloid leukemia reveals novel cryptic balanced translocations during disease progression.
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 35:2, s. 127-137
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Tidskriftsartikel (refereegranskat)abstract
- During the initial indolent chronic phase of chronic myeloid leukemia (CML), the t(9;22)(q34;q11), resulting in the Philadelphia chromosome (Ph), is usually the sole cytogenetic anomaly, but as the disease progresses into the accelerated phase (AP), and eventually into aggressive blast crisis (BC), secondary aberrations, mainly unbalanced changes such as +8, i(17q), and +Ph, are frequent. To date, molecular genetic studies of CML BC have mainly focused on alterations of well-known tumor-suppressor genes (e.g., TP53, CDKN2A, and RB1) and oncogenes (e.g., RAS and MYC), whereas limited knowledge is available about the molecular genetic correlates of the unbalanced chromosomal abnormalities. Balanced secondary changes are rare in CML AP/BC, but it is not known whether cryptic chromosomal translocations, generating fusion genes, may be responsible for disease progression in a subgroup of CML. To address this issue, we used multicolor combined binary ratio fluorescence in situ hybridization (FISH), which allows the simultaneous visualization of all 24 chromosomes in different colors, verified by locus-specific FISH in a series of 33 CML cases. Two cryptic balanced translocations, t(7;17)(q32-34;q23) and t(7;17)(p15;q23), were found in two of the five cases showing the t(9;22) as the only cytogenetic change. Using several BAC clones, the breakpoints at 17q23 in both cases were mapped within a 350-kb region. In the case with the 7p15 breakpoint, a BAC clone containing the HOXA gene cluster displayed a split signal, suggesting a possible creation of a fusion gene involving a member of the HOXA family. Furthermore, one case with a partially cryptic t(9;11)(p21-22;q23) and an MLL rearrangement as well as a previously unreported t(3;10)(p22;p12-13) were identified. Altogether, a refined karyotypic description was achieved in 12 (36%) of the 33 investigated cases, illustrating the value of using multicolor FISH for identifying pathogenetically important aberrations in CML AP/BC.
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| 2. |
- Gisselsson Nord, David, et al.
(författare)
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Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
- 2000
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 97:10, s. 5357-5362
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Tidskriftsartikel (refereegranskat)abstract
- It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression.
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| 3. |
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| 4. |
- Jin, Charlotte, et al.
(författare)
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Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 30:2, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.
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| 5. |
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| 6. |
- Johansson, Bertil, et al.
(författare)
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Isodicentric 7p, idic(7)(q11.2), in acute myeloid
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 30:3, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- Three adult de novo acute myeloid leukemias (AML M1, M2, and M4) with an isochromosome 7p are presented. No additional abnormalities were deterred by G-band and multicolor, using combined binary ratio labeling, fluorescence in situ hybridization (FISH) analyses, indicating that the i(7p) was the sole. i.e., the primary, chromosomal aberration. Although the patients were elderly-68, 72, and 78 years old-they all responded very well to chemotherapy, achieving complete remission lasting more than a year. Further FISH analyses, using painting, centromeric, as well as 7q11.2-specific YAC probes, revealed that the i(7p) contained two centromeres and that the breakpoints were located in 7q11.2. Thus, the abnormality should formally be designated idic(7)(q11.2). The detailed mapping disclosed a breakpoint heterogeneity, with the breaks in 7q11.2 varying among the cases, being at least 1,310 kb apart. Furthermore, the breakpoints also differed within one of the cases, being located on both the proximal and the distal side of the most centromeric probe used. Based on our three patients, as well as on a previously reported 82-year-old patient with AML M2 and idic(7)(q11) as the only chromosomal change, we suggest that this abnormality, as the sole anomaly, is associated with AML in elderly patients who display a good response to induction chemotherapy and. hence, have a favorable prognosis. Furthermore, the heterogeneous breakpoints in 7q11.2 suggest that the important functional outcome of the idic(7)(q11.2) is the genomic imbalance incurred, i.e., gain of 7p and loss of 7q material, rather than a rearrangement of a specific gene.
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| 7. |
- Lilienthal, Achim J., 1970-, et al.
(författare)
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Gas source declaration with a mobile robot
- 2004
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Ingår i: 2004 IEEE International Conference on Robotics and Automation. - New York, USA : IEEE. - 0780382323 ; , s. 1430-1435
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Konferensbidrag (refereegranskat)abstract
- As a sub-task of the general gas source localisation problem, gas source declaration is the process of determining the certainty that a source is in the immediate vicinity. Due to the turbulent character of gas transport in a natural indoor environment, it is not sufficient to search for instantaneous concentration maxima, in order to solve this task. Therefore, this paper introduces a method to classify whether an object is a gas source or not from a series of concentration measurements, recorded while the robot performs a rotation manoeuvre in front of a possible source. For three different gas source positions, a total of 288 declaration experiments were carried out at different robot-to-source distances. Based on these readings, two machine learning techniques (ANN, SVM) were evaluated in terms of their classification performance. With learning parameters that were optimised by grid search, a maximal hit rate of approximately 87.5% could be obtained using a support vector machine
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| 8. |
- Lilienthal, Achim J., 1970-, et al.
(författare)
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Learning to detect proximity to a gas source with a mobile robot
- 2004
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Ingår i: 2004 IEEE/RSJ international conference on intelligent robots and systems, 2004 (IROS 2004). - : Institute of Electrical and Electronics Engineers (IEEE). - 0780384636 ; , s. 1444-1449
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Konferensbidrag (refereegranskat)abstract
- As a sub-task of the general gas source localisation problem, gas source declaration is the process of determining the certainty that a source is in the immediate vicinity. Due to the turbulent character of gas transport in a natural indoor environment, it is not sufficient to search for instantaneous concentration maxima, in order to solve this task. Therefore, this paper introduces a method to classify whether an object is a gas source from a series of concentration measurements, recorded while the robot performs a rotation manoeuvre in front of a possible source. For three different gas source positions, a total of 1056 declaration experiments were carried out at different robot-to-source distances. Based on these readings, support vector machines (SVM) with optimised learning parameters were trained and the cross-validation classification performance was evaluated. The results demonstrate the feasibility of the approach to detect proximity to a gas source using only gas sensors. The paper presents also an analysis of the classification rate depending on the desired declaration accuracy, and a comparison with the classification rate that can be achieved by selecting an optimal threshold value regarding the mean sensor signal.
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| 9. |
- Nilsson, Therese, et al.
(författare)
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Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation
- 2002
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 68:6, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.
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| 10. |
- Ryde, Nils, et al.
(författare)
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The Zeeman-sensitive emission lines of MgI at 12 microns in Procyon
- 2004
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 617, s. 551-
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Tidskriftsartikel (refereegranskat)abstract
- Emission lines of magnesium at 12 mum have been observed in the spectrum of Procyon. We reproduce the observed disk-averaged line flux from Procyon ( as well as the observed intensity profiles from the Sun) by calculating the line formation and relaxing the assumption of local thermodynamic equilibrium. We find that the lines in Procyon are formed in the photosphere in the same manner as the solar lines. We discuss our modeling of these Rydberg lines and evaluate, among other things, the importance of the ionizing flux and updated model-atom parameters. The lines are of large diagnostic value for measurements of stellar magnetic fields through their Zeeman splitting. We have not, however, detected splitting of the Mg I lines in Procyon. Using simple arguments, we believe that we would have detected a magnetic field had it been of a strength larger than approximately 800 G covering more than a quarter of the surface. We discuss the prospects for future use of the Zeeman-sensitive, mid-infrared Mg I emission lines as a diagnostic tool for stellar magnetic fields.
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