High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma

Acral lentiginous melanoma (ALM) is a rare melanoma subtype primarily located in acral regions. However, ALMs exhibit a distinctive genetic profile characterized by a high number of copy number variations (CNVs) and limited point mutations. Late diagnosis and restricted therapeutic efficacy contribu...

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Detalles Bibliográficos
Autores: de la Rosa, Inés, Sisó Camarasa, Pol, Ríos, Christopher, Gracia, Judith, Cuevas Sánchez, Dolors, Maiques Carlos, Oscar, Eritja Sánchez, Núria, Soria, Xavier, Àngel Baldó, Joan, Gatius Calderó, Sònia, Sanchez-Moral, Lidia, Sarrias, Maria-Rosa, Matias-Guiu, Xavier, Martí Laborda, Rosa Ma., Macià Armengol, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/468510
Acceso en línea:https://doi.org/10.3390/ijms26094097
https://hdl.handle.net/10459.1/468510
Access Level:acceso abierto
Palabra clave:Acral lentiginous melanoma
Copy number variation
Tumor microenvironment
Secretome
Prognosis
Descripción
Sumario:Acral lentiginous melanoma (ALM) is a rare melanoma subtype primarily located in acral regions. However, ALMs exhibit a distinctive genetic profile characterized by a high number of copy number variations (CNVs) and limited point mutations. Late diagnosis and restricted therapeutic efficacy contribute to its poor prognosis. The secretome within the tumor microenvironment (TME) influences immune modulation and plays a vital role in melanoma progression. We aim to analyze the role of ALM secretome and CNVs profile with prognosis in primary ALM patients. Here, we demonstrated that high CNV burden (CNVsHigh) was associated with worse clinicopathological characteristics and poor prognosis. Furthermore, our study also revealed that conditioned media (CM) of CNVsHigh genetic profile ALM cell line was associated with pro-tumoral, pro-angiogenic, and immunosuppressive secretome profiles. In addition, CM of CNVsHigh cell lines in vitro promotes macrophage polarization to immunosuppressive phenotype. Moreover, we observed an increased presence of immunosuppressive tumor-associated macrophages (TAMs) at the invasive front (IF) of CNVsHigh ALM biopsies. This research reveals the adverse prognostic impact of CNVsHigh in ALM patients, establishing a novel link with a pro-tumor secretome, offering potential biomarkers for prognosis and personalized treatment to enhanced disease monitoring in ALM patients.

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