A melanoma és az agyi áttétképződés molekuláris                     háttere

Katona, Frida; Murnyák, Balázs; Markó-Varga, György; Hortobágyi, Tibor

doi:10.1556/650.2017.30793

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…Ultimately, it is the patients who suffer and experience the current limitations in treatment. From an international perspective, the biobanking developments within the Cancer Moonshot activities in Lund have thus been given top priority to provide high-quality and well-defined tissue and biofluid specimens [ 7 – 9 ]. The center includes pathological characterization, where the tumour tissues are evaluated with high integrity and in great detail, with annotations that relate to the types of cells presented in the tumour tissues, their nature, and the morphology captured by histology images.…”

Section: Introductionmentioning

confidence: 99%

Biobank integration of large‐scale clinical and histopathology melanoma studies within the European Cancer Moonshot Lund Center

Malm

Sugita²,

Szász

et al. 2018

Clinical & Translational Med

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We present the Cancer Moonshot clinical project located at the European center in Lund. Here, tissue and blood samples have been collected and stored in a large-scale biobank. Multiple clinical centers around the world are participating and tissue and blood samples are sent to the European Cancer Moonshot Lund Center that acts as the clinical hub. Our center has been developed to generate and build large-scale biostorage archives of patient melanoma samples, which is then combined with a histopathological capability to characterize the patient tumours. Such a large-scale clinical sample processing initiative has begun with the aim of creating high-end histopathology indexing with database computational power and including proteogenomic analysis. The biobank at Lund has become an important resource in clinical research worldwide. Following suite, several national health programs are being initiated with the aim of also building large-scale biobank storages with a wealth of high-quality patient samples. In our Cancer Moonshot R&D activities, samples in the biobanks and the data derived from these samples are being used to build an understanding of disease presentation and using this information to move towards ‘Big Data’ proteogenomic and mass spectrometry imaging studies. Additionally, we report here a sample processing workflow that has been adapted to a fully-automated biobank processing strategy for large-scale studies.

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Section: Introductionmentioning

confidence: 99%

Biobank integration of large‐scale clinical and histopathology melanoma studies within the European Cancer Moonshot Lund Center

Malm

Sugita²,

Szász

et al. 2018

Clinical & Translational Med

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“…Our research team initially developed manual preparation methods that were based on a thin-film technique that was generated using a multi-layer principle. By establishing an automated, highly-reproducible, thin-layer technology that could be applied to cancer tissues, a mass spectrometry (MALDI) sample target was produced from which high-resolution and high-sensitivity quantitation of drug compounds localised in patient tumours could be obtained [ 11 ]. The present study reveals experimental details on tumour tissue preparation technologies that provide optimal imaging properties of small molecule markers [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Endogenous expression mapping of malignant melanoma by mass spectrometry imaging

Sugita¹,

Rivas²,

Malm³

et al. 2018

Clinical & Translational Med

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Background Currently, only a limited number of molecular biomarkers for malignant melanoma exist. This is the case for both diagnosing the disease, staging, and efficiently measuring the response to therapy by tracing the progression of disease development and drug impact. There is a great need to identify novel landmarks of disease progression and alterations. Methods Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) has been developed within our group to study drug localisation within micro-environmental tissue compartments. Here, we expand further on this technology development and introduce for the first time melanoma tumour tissues to map metabolite localisation utilising high resolution mass spectrometry. MALDI-MSI can measure and localise the distribution pattern of a number of small molecule metabolites within tissue compartments of tumours isolated from melanoma patients. Data on direct measurements of metabolite identities attained at the local sites in tissue compartments has not been readily available as a measure of a clinical index for most cancer diseases. The current development on the mapping of endogenous molecular expression melanoma tumours by mass spectrometry imaging focuses on the establishment of a cancer tissue preparation process whereby a matrix crystal formation is homogenously built on the tissue surface, providing uniform molecular mapping. We apply this micro-preparation technology to disease presentation by mapping the molecular signatures from patient tumour sections. Results We have automated the process with a micro-technological dispensing platform. This provides the basis for thin film generation of the cancer patient tissues prior to imaging screening. Compartmentalisation of the tumour regions are displayed within the image analysis interfaced with histopathological grading and characterisation. Conclusions This enables site localisation within the tumour with image mapping to disease target areas such as melanoma cells, macrophages, and lymphocytes.

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Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases

Kraft

Grützmann

Meinhardt

et al. 2023

Sci Rep

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Melanomas frequently metastasize to distant organs and especially intracranial metastases still represent a major clinical challenge. Epigenetic reprogramming of intracranial metastases is thought to be involved in therapy failure, but so far only little is known about patient-specific DNA-methylation differences between intra- and extracranial melanoma metastases. Hierarchical clustering of the methylomes of 24 patient-matched intra- and extracranial melanoma metastases pairs revealed that intra- and extracranial metastases of individual patients were more similar to each other than to metastases in the same tissue from other patients. Therefore, a personalized analysis of each metastases pair was done by a Hidden Markov Model to classify methylation levels of individual CpGs as decreased, unchanged or increased in the intra- compared to the extracranial metastasis. The predicted DNA-methylation alterations were highly patient-specific differing in the number and methylation states of altered CpGs. Nevertheless, four important general observations were made: (i) intracranial metastases of most patients mainly showed a reduction of DNA-methylation, (ii) cytokine signaling was most frequently affected by differential methylation in individual metastases pairs, but also MAPK, PI3K/Akt and ECM signaling were often altered, (iii) frequently affected genes were mainly involved in signaling, growth, adhesion or apoptosis, and (iv) an enrichment of functional terms related to channel and transporter activities supports previous findings for a brain-like phenotype. In addition, the derived set of 17 signaling pathway genes that distinguished intra- from extracranial metastases in more than 50% of patients included well-known oncogenes (e.g. PRKCA, DUSP6, BMP4) and several other genes known from neuronal disorders (e.g. EIF4B, SGK1, CACNG8). Moreover, associations of gene body methylation alterations with corresponding gene expression changes revealed that especially the three signaling pathway genes JAK3, MECOM, and TNXB differ strongly in their expression between patient-matched intra- and extracranial metastases. Our analysis contributes to an in-depth characterization of DNA-methylation differences between patient-matched intra- and extracranial melanoma metastases and may provide a basis for future experimental studies to identify targets for new therapeutic approaches.

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A melanoma és az agyi áttétképződés molekuláris háttere

Cited by 4 publications

References 46 publications

Biobank integration of large‐scale clinical and histopathology melanoma studies within the European Cancer Moonshot Lund Center

Biobank integration of large‐scale clinical and histopathology melanoma studies within the European Cancer Moonshot Lund Center

Endogenous expression mapping of malignant melanoma by mass spectrometry imaging

Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases

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