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Dion Paridaens - One of the best experts on this subject based on the ideXlab platform.
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Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations.
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Kyra N. Smit, Robert M. Verdijk, Berna Beverloo, Hennie T. Brüggenwirth, Ronald Van Marion, Hendrikus J. Dubbink, Dion ParidaensAbstract:textabstractPURPOSE. Most of the Uvea Melanoma (UM) display a near-diploid (normal, ~2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM. METHODS. In 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing. RESULTS. Twenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P ¼ 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16- fold increased hazard ratio (HR 15.90, P = 0.009). CONCLUSIONS. The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.
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BAP1 correlates with metastasis in polyploid Uveal Melanoma
Acta Ophthalmologica, 2015Co-Authors: Emine Kilic, Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Nicole C. Naus, Dion Paridaens, A. De KleinAbstract:Purpose Most of the Uvea Melanoma (UM) display a near-diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes. Methods Fluorescence-In-Situ-Hybridization (FISH) and/or Single-Nucleotide-Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri- tetraploidy) were further investigated. Immune-histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing . Results Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow-up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008). Conclusions Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
Serdar Yavuzyigitoglu - One of the best experts on this subject based on the ideXlab platform.
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Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations.
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Kyra N. Smit, Robert M. Verdijk, Berna Beverloo, Hennie T. Brüggenwirth, Ronald Van Marion, Hendrikus J. Dubbink, Dion ParidaensAbstract:textabstractPURPOSE. Most of the Uvea Melanoma (UM) display a near-diploid (normal, ~2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM. METHODS. In 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing. RESULTS. Twenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P ¼ 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16- fold increased hazard ratio (HR 15.90, P = 0.009). CONCLUSIONS. The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.
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BAP1 correlates with metastasis in polyploid Uveal Melanoma
Acta Ophthalmologica, 2015Co-Authors: Emine Kilic, Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Nicole C. Naus, Dion Paridaens, A. De KleinAbstract:Purpose Most of the Uvea Melanoma (UM) display a near-diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes. Methods Fluorescence-In-Situ-Hybridization (FISH) and/or Single-Nucleotide-Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri- tetraploidy) were further investigated. Immune-histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing . Results Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow-up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008). Conclusions Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
A. De Klein - One of the best experts on this subject based on the ideXlab platform.
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BAP1 correlates with metastasis in polyploid Uveal Melanoma
Acta Ophthalmologica, 2015Co-Authors: Emine Kilic, Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Nicole C. Naus, Dion Paridaens, A. De KleinAbstract:Purpose Most of the Uvea Melanoma (UM) display a near-diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes. Methods Fluorescence-In-Situ-Hybridization (FISH) and/or Single-Nucleotide-Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri- tetraploidy) were further investigated. Immune-histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing . Results Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow-up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008). Conclusions Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
Jolanda Vaarwater - One of the best experts on this subject based on the ideXlab platform.
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Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations.
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Kyra N. Smit, Robert M. Verdijk, Berna Beverloo, Hennie T. Brüggenwirth, Ronald Van Marion, Hendrikus J. Dubbink, Dion ParidaensAbstract:textabstractPURPOSE. Most of the Uvea Melanoma (UM) display a near-diploid (normal, ~2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM. METHODS. In 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing. RESULTS. Twenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P ¼ 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16- fold increased hazard ratio (HR 15.90, P = 0.009). CONCLUSIONS. The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.
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BAP1 correlates with metastasis in polyploid Uveal Melanoma
Acta Ophthalmologica, 2015Co-Authors: Emine Kilic, Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Nicole C. Naus, Dion Paridaens, A. De KleinAbstract:Purpose Most of the Uvea Melanoma (UM) display a near-diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes. Methods Fluorescence-In-Situ-Hybridization (FISH) and/or Single-Nucleotide-Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri- tetraploidy) were further investigated. Immune-histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing . Results Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow-up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008). Conclusions Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
Hanneke W. Mensink - One of the best experts on this subject based on the ideXlab platform.
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Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations.
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Kyra N. Smit, Robert M. Verdijk, Berna Beverloo, Hennie T. Brüggenwirth, Ronald Van Marion, Hendrikus J. Dubbink, Dion ParidaensAbstract:textabstractPURPOSE. Most of the Uvea Melanoma (UM) display a near-diploid (normal, ~2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM. METHODS. In 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing. RESULTS. Twenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P ¼ 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16- fold increased hazard ratio (HR 15.90, P = 0.009). CONCLUSIONS. The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.
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BAP1 correlates with metastasis in polyploid Uveal Melanoma
Acta Ophthalmologica, 2015Co-Authors: Emine Kilic, Serdar Yavuzyigitoglu, Hanneke W. Mensink, Jolanda Vaarwater, Nicole C. Naus, Dion Paridaens, A. De KleinAbstract:Purpose Most of the Uvea Melanoma (UM) display a near-diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes. Methods Fluorescence-In-Situ-Hybridization (FISH) and/or Single-Nucleotide-Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri- tetraploidy) were further investigated. Immune-histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing . Results Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow-up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008). Conclusions Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
