The Experts below are selected from a list of 2220 Experts worldwide ranked by ideXlab platform
M J C Vader - One of the best experts on this subject based on the ideXlab platform.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation. For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi. Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.
Robert M Verdijk - One of the best experts on this subject based on the ideXlab platform.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation. For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi. Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.
Reinhard Dammann - One of the best experts on this subject based on the ideXlab platform.
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claudin11 promoter hypermethylation is frequent in malignant melanoma of the skin but uncommon in Nevus Cell nevi
Cancers, 2015Co-Authors: Sara K Walesch, Antje M Richter, Peter Helmbold, Reinhard DammannAbstract:Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma Cell lines, 39 primary melanoma, 41 metastases of MM and 52 Nevus Cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM Cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM Cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and Nevus Cell nevi.
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rassf10 promoter hypermethylation is frequent in malignant melanoma of the skin but uncommon in Nevus Cell nevi
Journal of Investigative Dermatology, 2012Co-Authors: Peter Helmbold, Sara K Walesch, Antje M Richter, Alexander Skorokhod, W C Marsch, Alexander Enk, Reinhard DammannAbstract:The Ras association domain family (RASSF) consists of several tumor suppressor genes, which are frequently silenced in human cancers. We analyzed the epigenetic inactivation of RASSF2 and RASSF10 in malignant melanoma (MM) of the skin, including 5 MM Cell lines, 28 primary MM, 33 metastases of MM, 47 Nevus Cell nevi (NCN), and 22 control tissues. The RASSF2 promoter was epigenetically downregulated in two MM Cell lines only, but not in any of the investigated tumor samples. In contrast, hypermethylation of the RASSF10 promoter was found in all investigated Cell lines, 19/28 (68%) of the primary MM and 30/33 (91%) of the MM metastases, 2/18 (11%) of the dysplastic NCN, and 0/29 (0%) of the non-dysplastic NCN (difference between MM and all nevi, P RASSF10 promoter hypermethylation correlated with a reduced RASSF10 mRNA expression in 3/4 MM Cell lines, and treatment with a DNA methylation inhibitor reactivated RASSF10 transcription. Furthermore, immunohistological RASSF10 expression corresponds negatively to its promoter methylation state. In summary, RASSF10 proved to be a characteristically epigenetically silenced tumor suppressor in melanomagenesis, and analysis of RASSF10 methylation status represents a new candidate tool to assist in discrimination between MM and NCN.
Karl H. Anders - One of the best experts on this subject based on the ideXlab platform.
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benign melanocytic Nevus Cells in axillary lymph nodes a prospective incidence and immunohistochemical study with literature review
American Journal of Clinical Pathology, 1994Co-Authors: Norman Bautista, Sylvan Cohen, Karl H. AndersAbstract:: Benign Nevus Cell aggregates (NCAs) in lymph nodes usually present as intracapsular or trabecular collections of small, uniform melanocytes that resemble those seen in intradermal melanocytic nevi. The surgical pathologist must be aware of nodal NCAs because they can mimic micrometastasis of carcinoma. Although not uncommon, the frequency with which NCAs occur is controversial. Two previous studies attempted to determine the case incidence of NCAs in axillary lymphadenectomies; widely different results were reported, ranging from .33% to 6.2%. In this study, the authors examined prospectively 300 axillary lymph node dissections containing 5186 lymph nodes, using S-100 protein immunohistochemistry as a supplemental evaluation measure, to determine the incidence of NCAs. Twenty-eight NCA-positive lymph nodes from 22 cases were found, for a 7.3% case incidence and a .54% nodal incidence; these figures were higher than those previously reported. The possible pathogenesis of this phenomenon is discussed, with a review of the literature.
Wilma Bergman - One of the best experts on this subject based on the ideXlab platform.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation. For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi. Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.
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gnaq and gna11 mutations and downstream yap activation in choroidal nevi
British Journal of Cancer, 2017Co-Authors: M J C Vader, Michele C Madigan, Mieke Versluis, H M Suleiman, G Gezgin, N A Gruis, Jacoba J Outluiting, Wilma Bergman, Robert M VerdijkAbstract:Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing Nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant Nevus Cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the Nevus Cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal Nevus Cells. We hypothesise that GNAQ/11 mutant-driven extraCellular mitogenic signalling involving YAP activation leads to accumulation of wild-type Nevus Cells.