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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88454 |
| Date | 05 December 2023 |
| Creators | 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 |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2072-6694, 10.3390/cancers14174066 |
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