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A novel patient-derived cutaneous melanoma cell line reveals key features of metastatic melanoma

2025Artigo científico Acesso aberto
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dc.contributor.authorTomás, Ana
dc.contributor.authorTomás, Ana
dc.contributor.authorRoque, Lúcia
dc.contributor.authorFrancisco, Inês
dc.contributor.authorSilva, Ana Luísa
dc.contributor.authorNunes, Hugo
dc.contributor.authorGouveia, Emanuel
dc.contributor.authorCarvalho, Elisabete
dc.contributor.authorFarricha, Victor
dc.contributor.authorMoura, Cecília
dc.contributor.authorRosa, Joaninha Costa
dc.contributor.authorCosta Rosa, Joaninha
dc.contributor.authorGarrido, Pedro Miguel
dc.contributor.authorAlbuquerque, Cristina
dc.contributor.authorPereira, Patrícia M.
dc.contributor.authorCabral, M. Guadalupe
dc.contributor.authorCabral, MG
dc.contributor.authorPojo, Marta
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblFrontiers Media
dc.date.accessioned2025-09-16T21:48:43Z
dc.date.available2025-09-16T21:48:43Z
dc.date.issued2025
dc.descriptionPublisher Copyright: Copyright © 2025 Tomás, Roque, Francisco, Silva, Nunes, Gouveia, Carvalho, Farricha, Moura, Rosa, Garrido, Albuquerque, Pereira, Cabral and Pojo.
dc.description.abstractIntroduction: Cutaneous melanoma (CM) is an aggressive form of skin cancer, with rising incidence and poor prognosis at advanced stages. While early-stage CM typically carries a favorable prognosis, a small subset of patients relapses and progresses to advanced disease, highlighting the need for a deeper understanding of CM biology. Here, we describe the establishment and characterization of a novel patient-derived primary cell line, MelT79, developed from a metastatic lesion of a patient initially diagnosed with stage IB CM, who unexpectedly progressed to advanced disease. Methods: MelT79 was characterized by multicolor fluorescence in situ hybridization, high resolution comparative genomic hybridization, and targeted next-generation sequencing. Gene and protein expression were evaluated by RT-qPCR and immunofluorescence, and cell proliferation was assessed using trypan blue exclusion and BrdU incorporation assays. Sensitivity to BRAF inhibition was measured with the Cell Counting Kit-8 viability assay. Gene and protein expression, proliferation, and drug sensitivity were compared to commercially available CM cell lines. Results: MelT79 exhibits a complex karyotype with significant chromosomal alterations, including deletions affecting key genes such as CDKN2A/B, SPRED1, and B2M, implicated in melanomagenesis and therapy resistance. Additionally, MelT79 harbors both the BRAF V600E mutation and a rare RET S649L mutation, which has not been previously reported in CM. RET S649L was also identified in an earlier metastatic lesion, possibly conferring a selective advantage, and highlighting this mutation as a potential therapeutic target. Phenotypically, MelT79 displays both differentiation and invasive traits, suggesting that its heterogeneity might contribute to progression and therapy resistance. Furthermore, the cell line exhibited moderate sensitivity to BRAF and MEK inhibitors when compared to other commercially available cell lines, reflecting its heterogeneity. Conclusion: MelT79 represents a valuable model for understanding CM heterogeneity, progression, and resistance mechanisms, offering new avenues for novel therapeutic interventions in CM.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2489190
dc.identifier.doi10.3389/fonc.2025.1531013
dc.identifier.issn2234-943X
dc.identifier.otherPURE: 129425890
dc.identifier.otherPURE UUID: a1690e66-30d3-474d-8515-cb5d17461c62
dc.identifier.otherScopus: 105012293224
dc.identifier.otherPubMed: 40756116
dc.identifier.urihttp://hdl.handle.net/10362/187987
dc.identifier.urlhttps://www.scopus.com/pages/publications/105012293224
dc.language.isoeng
dc.peerreviewedyes
dc.subjectcutaneous melanoma
dc.subjectimmunotherapy
dc.subjectphenotypic plasticity
dc.subjectprimary cell culture
dc.subjecttargeted therapy
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleA novel patient-derived cutaneous melanoma cell line reveals key features of metastatic melanomaen
dc.typejournal article
degois.publication.titleFrontiers in Oncology
degois.publication.volume15
dspace.entity.typePublication
person.familyNameTomás
person.familyNameCosta Rosa
person.familyNameCabral
person.givenNameAna
person.givenNameJoaninha
person.givenNameMaria de Guadalupe
person.identifier.ciencia-id8F16-85EE-447D
person.identifier.ciencia-id7D15-1016-4E4B
person.identifier.ciencia-idCB1B-C82A-D84A
person.identifier.orcid0000-0003-4710-2605
person.identifier.orcid0000-0002-3162-1876
person.identifier.orcid0000-0001-9016-9173
person.identifier.ridN-4029-2016
person.identifier.scopus-author-id55412398200
rcaap.rightsopenAccess
relation.isAuthorOfPublication8b3e2b26-c1f4-4328-8f4a-f94e43e0af28
relation.isAuthorOfPublicationa6c2f888-e480-48f5-b2a3-bc2a11b9d9b2
relation.isAuthorOfPublication08736bca-6978-4566-858b-b2edac1b2618
relation.isAuthorOfPublication.latestForDiscovery08736bca-6978-4566-858b-b2edac1b2618

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