30 research outputs found

    Additional file 2: of NephroCheck data compared to serum creatinine in various clinical settings

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    Description of the four additional patients as well as table and figure legends of table A, table B, figure A, figure B. (DOCX 18 kb

    Melanoma in association with a nevus in overview (A) and closeup (B).

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    <p>Immunohistochemically stained in (C) with the BRAF<sup>V600E</sup>-mutation specific antibody VE1. Benign(D) and malignant(F) parts of the tumor in closeup. E&G show sequencing result of the corresponding cuts.</p

    NRAS and BRAF Mutations in Melanoma-Associated Nevi and Uninvolved Nevi

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    <div><p>According to the prevailing multistep model of melanoma development, oncogenic BRAF or NRAS mutations are crucial initial events in melanoma development. It is not known whether melanocytic nevi that are found in association with a melanoma are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser microdissection we were able to selectively dissect and genotype cells either from the nevus or from the melanoma part of 46 melanomas that developed in association with a nevus. In 25 cases we also genotyped a control nevus of the same patients. Available tissue was also immunostained using the BRAF<sup>V600E</sup>-mutation specific antibody VE1. The BRAF<sup>V600E</sup> mutation was found in 63.0% of melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant differences in the distribution of BRAF or NRAS mutations could be found between melanoma and associated nevi or between melanoma associated nevi and control nevi. In concordant cases immunohistochemistry showed a higher expression (intensity of immunohistochemistry) of the mutated BRAF<sup>V600E</sup>-protein in melanomas compared to their associated nevi. In this series the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation. Our findings do not support the current traditional model of stepwise tumor progression.</p> </div

    Representative tumor parts of nevi groups.

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    <p>Melanoma associated nevi are more commonly strictly dermal and show less of the postulated features of so called "dysplastic" nevi.</p

    Comparison of mutation status between paired tumor groups.

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    <p>BRAF<sup>V600E</sup>-mutation status was evaluated by VE1-Immunohistochemistry and Sanger sequencing, NRAS<sup>Q61</sup> by Sanger sequencing alone. p-values denote two-tailed significance as measured by McNemar test.</p

    Table_1_DNA Methylation Associates With Clinical Courses of Atypical Meningiomas: A Matched Case–Control Study.xlsx

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    BackgroundAccounting for 15–20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. However, even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Recently, DNA methylation profiles showed their value for distinguishing biological behaviors in meningiomas. Therefore, aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas.MethodsAll patients that underwent resection of WHO grade II meningiomas between 1993 and 2015 were screened for a dismal course clinical course with ≥2 recurrences. These were matched to control cases with benign clinical courses without tumor recurrence. DNA methylation was assessed using the Infinium Methylation EPIC BeadChip microarray. Unsupervised hierarchical clustering was performed for identification of DNA methylation profiles associated with such a dismal clinical course.ResultsOverall, 11 patients with WHO grade II meningiomas with ≥2 recurrences (Group dismal) and matched 11 patients without tumor recurrence (Group benign) were identified. DNA methylation profiles revealed 3 clusters—one comprising only patients of group dismal, a second cluster comprising mainly patients from group benign and a third cluster comprising one group dismal and one group benign patient. Based on differential methylation pattern associations with the Wnt and the related cadherin signaling pathway was observed.ConclusionDNA methylation clustering showed remarkable differences between two matched subgroups of WHO grade II meningiomas. Thus, DNA methylation profiles may have the potential to support prognostic considerations regarding meningioma recurrence and radiotherapeutic treatment allocation after surgical resection.</p

    DataSheet_1_DNA Methylation Associates With Clinical Courses of Atypical Meningiomas: A Matched Case–Control Study.docx

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    BackgroundAccounting for 15–20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. However, even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Recently, DNA methylation profiles showed their value for distinguishing biological behaviors in meningiomas. Therefore, aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas.MethodsAll patients that underwent resection of WHO grade II meningiomas between 1993 and 2015 were screened for a dismal course clinical course with ≥2 recurrences. These were matched to control cases with benign clinical courses without tumor recurrence. DNA methylation was assessed using the Infinium Methylation EPIC BeadChip microarray. Unsupervised hierarchical clustering was performed for identification of DNA methylation profiles associated with such a dismal clinical course.ResultsOverall, 11 patients with WHO grade II meningiomas with ≥2 recurrences (Group dismal) and matched 11 patients without tumor recurrence (Group benign) were identified. DNA methylation profiles revealed 3 clusters—one comprising only patients of group dismal, a second cluster comprising mainly patients from group benign and a third cluster comprising one group dismal and one group benign patient. Based on differential methylation pattern associations with the Wnt and the related cadherin signaling pathway was observed.ConclusionDNA methylation clustering showed remarkable differences between two matched subgroups of WHO grade II meningiomas. Thus, DNA methylation profiles may have the potential to support prognostic considerations regarding meningioma recurrence and radiotherapeutic treatment allocation after surgical resection.</p
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