Analysis of monosomy‐3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients

Tura, Aysegül; Merz, Hartmut; Reinsberg, Mihaela; Lüke, Matthias; Jager, Martine J.; Grisanti, Salvatore; Lüke, Julia

doi:10.1111/pcmr.12507

Cited by 39 publications

(36 citation statements)

References 51 publications

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“…One recent study combined the isolation of CTCs with the same technology with immuno-FISH detection of monosomy of chromosome 3 in 44 primary UM patients. Monosomy 3 was detected in intact CTCs of 58% of patients and was confirmed in the primary tumor of 10 out of 11 tested patients [338]. These results suggest that the FISH–cytogenetics of CTCs might provide useful prognostic information, particularly in UM patients not undergoing surgery or biopsy.…”

Section: Biomarkersmentioning

confidence: 93%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

193

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Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.

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Section: Biomarkersmentioning

confidence: 93%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

193

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“…Moreover, extensive researches also suggest that UM with monosomy 3 is associated with a dramatically poor prognosis, which consistent with our research. [18][19][20] The subgroups analysis of Chromosome.3.status showed that the percentage of Monosomy 3 in C1 molecular subgroup is much higher than this in C2 molecular subtype ( Table 1). The different analysis of m6A regulators between C1/2 molecular subtype showed that "eraser" like ALKBH5, "writer" like METTL3, METTL14, and WTAP and "readers", like YTHDF1 and YTHDF2 have signi cant differences.…”

Section: Discussionmentioning

confidence: 99%

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

Tang

Wan

2020

Preprint

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Abstract Purpose: The aim of this study was to identify gene signatures and prognostic values of m6A methylation regulators in uveal melanoma (UM). Methods: The RNA sequencing dataset and corresponding clinical information were downloaded from TCGA and GEO database. Based on the expression of m6A RNA methylation regulators , the patients were further clustered into different groups by applying the “ClassDiscovery” algorithm. Best survival analysis was performed to select prognostic m6A regulators and multivariate cox regression analysis was applied to constructed m6A regulators signature. The association between mutations and m6A regulators was assessed by Kruskal−Wallis tests and clinical characteristics were examined by using chi-square test. Result: Totally, we identified two molecular subtypes of UM (C1/2) by applying consensus clustering to m6A RNA methylation regulators. In contrast to the C1 subtype, the C2 subtype associates with a better prognosis, have higher percentage of subtype 1 and lower percentage of Monosomy 3 which have been regarded as the well established prognostic markers for UM. The malignant hallmarks of mTORC1 signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype. Moreover, a 3 - m6A regulators signature was constructed by multivariate cox regression analysis method, which closely correlated with chromosome 3 status, subtype 1 of UM and can robustly predict patients’ overall survival time. Conclusions: m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of UM and might be regarded as a new promising biomarker for UM prognosis and treatment strategy development.

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“…Der Vorteil dieser Methode ist die Möglichkeit weiterer Untersuchun-gen wie z. B. die geno-und phänotypische Charakterisierung [29][30][31]. Mit unserer Methodik werden ZMZs mittels an Immunobeads gekoppelten Antikörpern, die gegen verschiedene melanomspezifische Antigene gerichtet sind, aus dem Blut isoliert.…”

Section: Nachweismethoden Zirkulierender Melanomzellen (Zmz) Bei Chorunclassified

“…Dies entspricht einer Dichte von 3,5 Zellen/10 ml Blut (Spannweite: 0-12,8 Zellen) [29]. Unabhängig von der verwendeten Technik der immunomagnetischen Isolation besteht bei allen Verfahren die Schwierigkeit der exakten Identifikation und Abgrenzung der isolierten Zellen, insbesondere zu den Leukozyten [31]. Durch eine Doppelimmunfärbung gegen das Leukozytenantigen CD45 und gegen die Melanommarker NKI/C3 bzw.…”

Section: Nachweismethoden Zirkulierender Melanomzellen (Zmz) Bei Chorunclassified

“…Außerdem wiesen alle Patienten, die im weiteren Verlauf metastasierten, Monosomie-3-positive ZMZs auf. Zudem konnten wir in 10 von 11 Fällen eine Übereinstimmung des Monosomie-3-Status der zirkulierenden Melanomzellen mit dem Primärtumor feststellen [31]. Die Bestimmung dieser chromosomalen Aberration der ZMZs lässt somit Rückschlüsse auf den Primärtumor zu und lässt sich als nicht invasives und wiederholbares Instrument (im Vergleich zur Probebiopsie) einsetzen.…”

Section: Nachweismethoden Zirkulierender Melanomzellen (Zmz) Bei Chorunclassified

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Potenziale und Limitationen der Detektion von zirkulierenden Melanomzellen

Lüke

Grisanti

Tura

2017

Klin Monatsbl Augenheilkd

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The detection and characterisation of circulating melanoma cells (CMC) is a non-invasive procedure with a low complication rate and can potentially distinguish choroidal nevi from uveal melanomas and help to initiate early adequate therapy. It has the perspective to select and monitor treatment. This technique may lead to new insights into the metastasis process itself and help to detect specific targets for future therapies. This article introduces the different techniques for CMC detection; their potentials and limitations are discussed.

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Analysis of monosomy‐3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients

Cited by 39 publications

References 51 publications

The biology of uveal melanoma

The biology of uveal melanoma

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

Potenziale und Limitationen der Detektion von zirkulierenden Melanomzellen

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