Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors
| العنوان: | Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors |
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| المؤلفون: | Anne Zaremba, Philipp Jansen, Rajmohan Murali, Anand Mayakonda, Anna Riedel, Manuel Philip, Christian Rose, Jörg Schaller, Hansgeorg Müller, Heinz Kutzner, Inga Möller, Nadine Stadtler, Julia Kretz, Antje Sucker, Agnes Bankfalvi, Elisabeth Livingstone, Lisa Zimmer, Susanne Horn, Annette Paschen, Christoph Plass, Dirk Schadendorf, Eva Hadaschik, Pavlo Lutsik, Klaus Griewank |
| المصدر: | International Journal of Cancer. 151:1542-1554 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Diagnosis, Differential, Paraganglioma, Cancer Research, Skin Neoplasms, DNA Copy Number Variations, Oncology, Nevus, Epithelioid and Spindle Cell, Medizin, Humans, Syndrome, Melanoma, Methylation |
| الوصف: | in press Accurate classification of melanocytic tumors is important for prognostic evaluation, treatment and follow-up protocols of patients. The majority of melanocytic proliferations can be classified solely based on clinical and pathological criteria, however in select cases a definitive diagnostic assessment remains challenging and additional diagnostic biomarkers would be advantageous. We analyzed melanomas, nevi, Spitz nevi and atypical spitzoid tumors using parallel sequencing (exons of 611 genes and 507 gene translocation analysis) and methylation arrays (850k Illumina EPIC). By combining detailed genetic and epigenetic analysis with reference-based and reference-free DNA methylome deconvolution we compared Spitz nevi to nevi and melanoma and assessed the potential for these methods in classifying challenging spitzoid tumors. Results were correlated with clinical and histologic features. Spitz nevi were found to cluster independently of nevi and melanoma and demonstrated a different mutation profile. Multiple copy number alterations and TERT promoter mutations were identified only in melanomas. Genome-wide methylation in Spitz nevi was comparable to benign nevi while the Leukocytes UnMethylation for Purity (LUMP) algorithm in Spitz nevi was comparable to melanoma. Histologically difficult to classify Spitz tumor cases were assessed which, based on methylation arrays, clustered between Spitz nevi and melanoma and in terms of genetic profile or copy number variations demonstrated worrisome features suggesting a malignant neoplasm. Comprehensive sequencing and methylation analysis verify Spitz nevi as an independent melanocytic entity distinct from both nevi and melanoma. Combined genetic and methylation assays can offer additional insights in diagnosing difficult to classify Spitzoid tumors. |
| تدمد: | 1097-0215 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45e4a01f5cb504d29049ec8be3718523Test https://doi.org/10.1002/ijc.34187Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....45e4a01f5cb504d29049ec8be3718523 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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