A malignus melanoma genetikai sokszínűsége és immunológiai jellemzői a terápiás paletta tükrében

Malignant melanoma, originating from pigment cells, is a highly aggressive tumour affecting patients of any age group. Its incidence is rapidly growing. The most common form can be easily diagnosed by any physician. There are some well-known genetic (skin-, eye-, hair colour, naevi, melanoma in the personal/family history) and environmental (ultraviolet radiation) predisposing factors. Treatment is based on early diagnosis and excision. When metastasis occurs, the traditional chemo- and radiotherapy gives a low response rate. Recently some newly approved targeted therapies and immunomodulant drugs have become available. This review focuses on the classification and novel therapeutic approaches of malignant melanoma to provide guidance to clinicians. Orv. Hetil., 2015, 156(15), 583-591

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease

Organ specific copy number variations in visceral metastases of human melanoma

Malignant melanoma is one of the most aggressive skin cancers with high potential of visceral dissemination. Since the information about melanoma genomics is mainly based on primary tumors and lymphatic or skin metastases, an autopsy-based visceral metastasis biobank was established. We used copy number variation arrays (N = 38 samples) to reveal organ specific alterations. Results were partly completed by proteomic analysis. A significant increase of high-copy number gains was found in an organ-specific manner, whereas copy number losses were predominant in brain metastases, including the loss of numerous DNA damage response genes. Amplification of many immune genes was also observed, several of them are novel in melanoma, suggesting that their ectopic expression is possibly underestimated. This “immunogenic mimicry” was exclusive for lung metastasis. We also provided evidence for the possible autocrine activation of c-MET, especially in brain and lung metastases. Furthermore, frequent loss of 9p21 locus in brain metastases may predict higher metastatic potential to this organ. Finally, a significant correlation was observed between BRAF gene copy number and mutant allele frequency, mainly in lung metastases. All of these events may influence therapy efficacy in an organ specific manner, which knowledge may help in alleviating difficulties caused by resistance

The Driverless Triple-Wild-Type (BRAF, RAS, KIT) Cutaneous Melanoma: Whole Genome Sequencing Discoveries

The genetic makeup of the triple-wild-type melanoma (BRAF, NRAS and NF1) has been known for some time, but those studies grouped together rare histopathological versions with common ones, as well as mucosal and even uveal ones. Here we used whole genome sequencing to genetically characterize the triple-wild-type melanoma (TWM), termed here as BRAF, RAS and KIT wild type (the most frequent oncogenic drivers of skin melanoma), using the most common histological forms and excluding rare ones. All these tumors except one were clearly induced by UV based on the mutational signature. The tumor mutational burden was low in TWM, except in the NF1 mutant forms, and a relatively high frequency of elevated LOH scores suggested frequent homologue recombination deficiency, but this was only confirmed by the mutation signature in one case. Furthermore, all these TWMs were microsatellite-stabile. In this driverless setting, we revealed rare oncogenic drivers known from melanoma or other cancer types and identified rare actionable tyrosine kinase mutations in NTRK1, RET and VEGFR1. Mutations of TWM identified genes involved in antitumor immunity (negative and positive predictors of immunotherapy), Ca++ and BMP signaling. The two regressed melanomas of this cohort shared a 17-gene mutation signature, containing genes involved in antitumor immunity and several cell surface receptors. Even with this comprehensive genomic approach, a few cases remained driverless, suggesting that unrecognized drivers are hiding among passenger mutations

Badanie aktywności fizycznej i nawyków konsumpcji sportowej wśród studentów

Background. Adequate level of physical activity helps and provides optimal body function. Understanding the sports consumption and physical activity indicators of young adults helps to develop strategies that can help to understand the economic and health background of endemic diseases. Material and methods. We conducted cross-sectional research at the University of Pécs, Hungary, in 2018. We used an anonymous, self-edited, self-administered online questionnaire. The questions related to demographics, physical activity, sport and health motivation, and lifestyle. Our aim was to characterize the physical activity and sports consumption habits of the students. Results. In terms of health status and quality of life, the whole sample (n=197) marked theirs as better than average. In the case of sports motivation, we hypothesized that there would be a significant difference between gender; apart from fitness status (p=0.64), we found significantly different motivation levels in each case. In terms of physical activity, women were more engaged in housework and transport, whilst men were more active in free time and work. Conclusions. Our sample’s health status and quality of life is adequate. Men’s physical activity exceeds women, however, when comparing activity-related MET (metabolic equivalent of task) between the sexes, we did not find significant differences in any case (p≥0.05).Wprowadzenie. Odpowiedni poziom aktywności fizycznej wspomaga i zapewnia optymalne funkcjonowanie organizmu. Zrozumienie wskaźników konsumpcji sportowej oraz aktywności fizycznej wśród młodych dorosłych pomaga opracować strategie, które mogą pomóc określić ekonomiczne i zdrowotne źródła chorób endemicznych. Materiał i metody. W 2018 roku przeprowadziliśmy badania przekrojowe na Uniwersytecie w Peczu (Węgry). Wykorzystaliśmy anonimowy, samodzielnie zredagowany i wypełniany kwestionariusz internetowy. Pytania dotyczyły demografii, aktywności fizycznej, motywacji dotyczącej sportu i zdrowia oraz stylu życia. Naszym celem było scharakteryzowanie aktywności fizycznej i nawyków konsumpcji sportowej studentów. Wyniki. Pod względem stanu zdrowia i jakości życia wszyscy respondenci (n=197) ocenili swój stan powyżej środkowej wartości skali. W przypadku motywacji dotyczącej sportu postawiliśmy hipotezę, że istnieje znacząca różnica między płciami w zakresie czynników motywacyjnych. W każdym przypadku poza wskaźnikiem stanu sprawności (p=0,64) stwierdziliśmy istotnie odmienne poziomy motywacji. Kobiety wykazały większą aktywność fizyczną w pracach domowych i transporcie, a mężczyźni – w czasie wolnym oraz podczas pracy. Wnioski. Stan zdrowia respondentów i ich jakość życia są właściwe. Aktywność fizyczna mężczyzn przewyższa aktywność fizyczną kobiet. Podczas porównywania ekwiwalentu metabolicznego (MET) związanego z aktywnością obu płci nie stwierdziliśmy jednak istotnej różnicy w żadnym przypadku (p≥0,05)