What question did this study set out to answer?

The aim is to understand the genomic differences between primary and metastatic melanoma tumors.

May 30, 2026

Genomic differences between primary and metastatic melanoma: Insights from AACR GENIE.

Key Points

The aim is to understand the genomic differences between primary and metastatic melanoma tumors.
Data was extracted from the AACR Project GENIE v.18.0 database.
A comparison of genomic alterations in primary versus metastatic melanoma samples was conducted.
Samples with unclear tumor sites were excluded from the analysis.
In primary tumors, the most frequent mutations were found in BRAF (32%) and TERT (28.5%).
In metastatic tumors, TERT mutations were more frequent at 44%, followed by BRAF at 37.9%.
Copy number alterations in CDKN2A were found in 19.2% of primary tumors and 23.5% of metastatic tumors.

Abstract

e21585 Background: Melanoma is a highly aggressive malignancy that is characterized by a complex and heterogeneous genomic profile. The most common somatic driver mutations occur in the BRAF, NRAS, and NF1 genes. KIT mutations are also frequent in acral and mucosal melanoma. Genomic profiling is integral to melanoma management as it guides the use of targeted therapies especially in the metastatic setting. The variation in genomic profile between primary and metastatic tumors is poorly understood and can have implications in patient’s care. Methods: We utilized the AACR Project GENIE v.18.0 database to extract data from patients with a malignant melanoma diagnosis. We compared the genomic alterations identified in samples obtained from primary tumors versus those obtained from metastatic tumors. Samples with unclear site (primary vs metastatic) were excluded from analysis. Only genes sequenced in more than one fourth of each category were included in the analysis. Results: We included a total of 8,142 samples (3,277 samples obtained from primary tumors and 4,865 samples obtained from metastatic tumors). In primary tumor samples, the most frequent gene mutations were found in the BRAF (32%, n = 1049), TERT (28.5%, n = 634), NRAS (22.5%, n = 737), and NF1 (21.3%, n = 463) genes. The most frequent copy number alterations were identified in the CDKN2A (19.2%, n = 306), CDKN2B (15.3%, n = 243), and MTAP genes (9.5%, n = 82). The most common structural variants were seen in the BRAF (1.0%, n = 21), CDKN2A (0.8%, n = 16) and NF1 genes (0.8%, n = 17). In metastatic tumor samples, the most frequent gene mutations were found in the TERT (44%, n = 1,494), BRAF (37.9%, n = 1,843), NRAS (25.5%, n = 1,239), and NF1 (23.4%, n = 788) genes. The most frequent copy number alterations were identified in the CDKN2A (23.5%, n = 645), CDKN2B (17.9%, n = 490), and MTAP genes (10%, n = 130). The most common structural variants were seen in the BRAF (1.9%, n = 61), NF1 (0.7%, n = 22), and RAF1 genes (0.5%, n = 16). Variations according to melanoma subtypes were observed and were consistent with the overall analysis. Conclusions: While similarity exists in the molecular profile of primary and metastatic melanoma samples, relative variations in prevalence highlights the importance of sequential testing. The confounding role of prior targeted therapy in the adjuvant setting and prognostic role of some genomic alterations cannot be excluded.

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Cite This Study

Wahb et al. (Thu,) studied this question.

synapsesocial.com/papers/6a1a7fce0307b78509431ef4 https://doi.org/https://doi.org/10.1200/jco.2026.44.16_suppl.e21585

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