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Organ specific copy...
Organ specific copy number variations in visceral metastases of human melanoma
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- Papp, Orsolya (författare)
- Semmelweis University
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- Doma, Viktória (författare)
- Semmelweis University
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- Gil, Jeovanis (författare)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Markó-Varga, György (författare)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups,Tokyo Medical University,Yonsei University
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- Kárpáti, Sarolta (författare)
- Semmelweis University
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- Tímár, József (författare)
- Semmelweis University
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- Vízkeleti, Laura (författare)
- Semmelweis University
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(creator_code:org_t)
- 2021-11-28
- 2021
- Engelska.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:23
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.mdpi.com...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- BRAF and NRAS mutant allele frequency
- DDR deficiency
- Distant organ metastasis
- HGF/MET autocrine activation
- Immunogenic mimicry
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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