| Autor: |
Zaremba, Anne, Jansen, Philipp, Murali, Rajmohan, Mayakonda, Anand, Riedel, Anna, Krahl, Dieter, Burkhardt, Hans, John, Stefan, Géraud, Cyrill, Philip, Manuel, Kretz, Julia, Möller, Inga, Stadtler, Nadine, Sucker, Antje, Paschen, Annette, Ugurel, Selma, Zimmer, Lisa, Livingstone, Elisabeth, Horn, Susanne, Plass, Christoph, Schadendorf, Dirk, Hadaschik, Eva, Lutsik, Pavlo, Griewank, Klaus |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Druh dokumentu: |
Článek |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers14174066 |
| Popis: |
Melanocytic neoplasms have been genetically characterized in detail during the last decade. Recurrent CTNNB1 exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology. In addition, they have been identified in 1–2% of advanced melanoma. Performing a detailed genetic analysis of difficult-to-classify nevi and melanomas with CTNNB1 mutations, we found that benign tumors (nevi) show characteristic morphological, genetic and epigenetic traits, which distinguish them from other nevi and melanoma. Malignant CTNNB1-mutant tumors (melanomas) demonstrated a different genetic profile, instead grouping clearly with other non-CTNNB1 melanomas in methylation assays. To further evaluate the role of CTNNB1 mutations in melanoma, we assessed a large cohort of clinically sequenced melanomas, identifying 38 tumors with CTNNB1 exon 3 mutations, including recurrent S45 (n = 13, 34%), G34 (n = 5, 13%), and S27 (n = 5, 13%) mutations. Locations and histological subtype of CTNNB1-mutated melanoma varied; none were reported as showing deep penetrating nevus-like morphology. The most frequent concurrent activating mutations were BRAF V600 (n = 21, 55%) and NRAS Q61 (n = 13, 34%). In our cohort, four of seven (58%) and one of nine (11%) patients treated with targeted therapy (BRAF and MEK Inhibitors) or immune-checkpoint therapy, respectively, showed disease control (partial response or stable disease). In summary, CTNNB1 mutations are associated with a unique melanocytic tumor type in benign tumors (nevi), which can be applied in a diagnostic setting. In advanced disease, no clear characteristics distinguishing CTNNB1-mutant from other melanomas were observed; however, studies of larger, optimally prospective, cohorts are warranted. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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