The human melanoma proteome atlas—Defining the molecular pathology

Betancourt, Lázaro; Gil, Jeovanis; Kim, Yonghyo; Doma, Viktória; Çakır, Uğur; Sánchez, Aniel; Murillo, Jimmy Rodriguez; Kuras, Magdalena; Pla, Indira; Sugita, Y.; Appelqvist, Roger; Wieslander, Elisabet; Welinder, Charlotte; Velásquez, Erika; Almeida, Natália Pinto de; Woldmar, Nicole; Marko-Varga, Matilda; Pawłowski, Krzysztof; Eriksson, Jonatan; Szeitz, Beáta; Baldetorp, Bo; Ingvar, Christian; Olsson, Håkan; Lundgren, Lotta; Lindberg, Henrik; Oskolás, Henriett; Lee, Boram; Berge, Ethan; Sjögren, Marie; Eriksson, Carina; Kim, Dasol; Kwon, Ho Jeong; Knudsen, Beatrice S.; Rezeli, Melinda; Hong, Runyu; Horvatovich, Péter; Miliotis, Tasso; Nishimura, Toshihide; Kato, Harubumi; Steinfelder, Erik; Oppermann, Madalina; Miller, Ken; Florindi, Francesco; Zhou, Qimin; Domont, Gilberto B.; Pizzatti, Luciana; Nogueira, Fábio César Sousa; Horváth, Péter; Szadai, Leticia; Tı́már, József; Kárpáti, Sarolta; Szász, Attila Marcell; Malm, Johan; Fenyö, David; Ekedahl, Henrik; Németh, István; Markó-Varga, György

doi:10.1002/ctm2.473

Cited by 18 publications

(28 citation statements)

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“…The transcript data from 443 melanomas were curated and processed from the Cancer Genome Atlas (TCGA) repositories [ 15 ]. The clinical protein expression profiles were generated from a prospective, and a postmortem study cohort, recently presented within the Human Melanoma Proteome Atlas [ 16 , 17 ]. In summary, only one out of 19 amplified immunogenic mimicry (IGM) genes (CD172) was not detected at transcript levels in TCGA, while at the protein level, 10 proteins were identified in each proteomics cohort.…”

Section: Resultsmentioning

confidence: 99%

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Organ Specific Copy Number Variations in Visceral Metastases of Human Melanoma

Papp

Doma

Gil

et al. 2021

Cancers

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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.

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Section: Resultsmentioning

confidence: 99%

“…All the experiments were performed within the “Human Melanoma Proteome Atlas” project as described previously [ 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

Organ Specific Copy Number Variations in Visceral Metastases of Human Melanoma

Papp

Doma

Gil

et al. 2021

Cancers

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“…Tumors were snap-frozen and stored at −80 °C. Frozen tissue pieces were sliced for histological characterization and omic analysis at a fix 10 μm thickness, as previously described [ 14 , 16 ]. Briefly, 15 consecutive slices (10 μm thickness) were collected for proteomics and PTM analysis while the previous and following sections were placed on glass slides and stained with hematoxylin and eosin (H&E).…”

Section: Methodsmentioning

confidence: 99%

“…With a special emphasis on the protein and post-translational modification (PTM) level, it is now possible to identify and quantify thousands of PTM events from minute amounts of starting material in melanoma tissue [ 10 , 11 , 12 , 13 , 14 ]. In particular, by integrating in-depth proteomics and PTMs, detailed histopathological characterization assisted by an AI algorithm and clinical information on 500 melanoma samples, our group presented the first blueprint of the Human Melanoma Proteome Atlas [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

An Observational Study on the Molecular Profiling of Primary Melanomas Reveals a Progression Dependence on Mitochondrial Activation

Gil

Rezeli

Lutz

et al. 2021

Cancers

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Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.

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“…For example, more human disease proteome alterations have been mapped and uncovered by combining in‐depth histopathology with proteome characterization, protein levels with multiple localizations, chromosomal and subcellular distributions with organ/tissue function, and protein profiles with clinical phenomes. 9 , 10 The package of protein discovery includes the identification of peptide spectrum matches, protein‐coding genes, peptides, sites of phosphorylation and acetylation, crossing networks among multiomics, spatiotemporal localization, mutations, splice isoforms, and variants in diseases. The combination of RNA and protein discoveries has made significant contributions to our understanding of disease and developing new vaccinations and neutralizations in the coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).…”

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confidence: 99%

Discovery in clinical and translational medicine

Wang

Wang²

2021

Clinical & Translational Med

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With the rapid development of biotechnologies and deep improvement of knowledge, “Discovery” is the initial period and source of innovation of clinical and translational medicine. The international journal of Clinical and Translational Discovery serves to highlight unknown or unclear aspects of clinical and translational medicine‐associated knowledge, technologies, mechanisms, and therapies (https://onlinelibrary.wiley.com/journal/27680622). The Discovery aims to define the interaction between genes, proteins, and cells, and explore molecular mechanisms of intercommunication and inter‐regulation. More discoveries of technologies and equipment are expected to improve method sensitivity, specificity, stability, analysis, and clinical significance. The first priority of Clinical and Translational Discovery is to turn gene‐, protein‐, drug‐, cell‐, and interaction‐based discoveries into health advancements. Clinical and Translational Discovery highly focuses on the discoveries of biological therapies and precision medicine‐based therapy elicited from computational chemistry, DNA libraries, target‐dependent small molecular drugs, high‐throughput screening, vaccination, immune therapy, cell implantations, gene editing, and RNA‐ or protein‐based inhibitors. Thus, Clinical and Translational Discovery sincerely welcome you to join and share the rapid development and future successes to come.

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The human melanoma proteome atlas—Defining the molecular pathology

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 65 publications

Organ Specific Copy Number Variations in Visceral Metastases of Human Melanoma

Organ Specific Copy Number Variations in Visceral Metastases of Human Melanoma

An Observational Study on the Molecular Profiling of Primary Melanomas Reveals a Progression Dependence on Mitochondrial Activation

Discovery in clinical and translational medicine

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