Interdependence of Molecular Lesions That Drive Uveal Melanoma Metastasis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37958591", "kind": "science-record", "revision": 5, "content_hash": "sha256:2abe1181dd036d1fc0b6a319d0b02f5cc954a69efcd43fc164660e3642f59300", "created_at": "2026-11-01T19:02:51Z", "updated_at": "2026-11-01T22:53:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Interdependence of Molecular Lesions That Drive Uveal Melanoma Metastasis.", "doi": "10.3390/ijms242115602", "pmid": "37958591", "authors": ["Francesco Reggiani", "Marianna Ambrosio", "Michela Croce", "Enrica Teresa Tanda", "Francesco Spagnolo", "Edoardo Raposio", "Mariangela Petito", "Zeinab El Rashed", "Alessandra Forlani", "Ulrich Pfeffer", "Adriana Agnese Amaro"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "The metastatic risk of uveal melanoma (UM) is defined by a limited number of molecular lesions, somatic mutations (SF3B1 and BAP1), and copy number alterations (CNA): monosomy of chromosome 3 (M3), chr8q gain (8q), chr6p gain (6p), yet the sequence of events is not clear. We analyzed data from three datasets (TCGA-UVM, GSE27831, GSE51880) with information regarding M3, 8q, 6p, SF3B1, and BAP1 status. We confirm that BAP1 mutations are always associated with M3 in high-risk patients. All other features (6p, 8q, M3, SF3B1 mutation) were present independently from each other. Chr8q gain was frequently associated with chr3 disomy. Hierarchical clustering of gene expression data of samples with different binary combinations of aggressivity factors shows that patients with 8q|M3, BAP1|M3 form one cluster enriched in samples that developed metastases. Patients with 6p combined with either 8q or SF3B1 are mainly represented in the other, low-risk cluster. Several gene expression events that show a non-significant association with outcome when considering single features become significant when analyzing combinations of risk features indicating additive action. The independence of risk factors is consistent with a random risk model of UM metastasis without an obligatory sequence.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes were computed with the Limma R package [53]. We used the NEMO R package [42], selecting k = 4, to perform Data Fusion on the Uveal Melanoma dataset. The relationship between gene expression and mean methylation levels was computed in R, using the Pearson Correlation Coefficient (PCC), associated p-value was computed with the cor.test R function, all values are reported in Table S1. Significance of survival curves was computed with the Log-rank test, using the surv_pvalue function of the Survminer R package [54,55], p-values are reported in Table S2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37958591", "locator": "sections[9] \"4.3. UM Expression Data Analysis\" paragraph 2", "quote": "Differentially expressed genes were computed with the Limma R package [53]."}, {"asset": "source:pmid:37958591", "locator": "sections[9] \"4.3. UM Expression Data Analysis\" paragraph 2", "quote": "We used the NEMO R package [42], selecting k = 4, to perform Data Fusion on the Uveal Melanoma dataset."}, {"asset": "source:pmid:37958591", "locator": "sections[10] \"4.4. Statistical Analysis\" paragraph 2", "quote": "The relationship between gene expression and mean methylation levels was computed in R, using the Pearson Correlation Coefficient (PCC), associated p-value was computed with the cor.test R function, all values are reported in Table S1."}, {"asset": "source:pmid:37958591", "locator": "sections[10] \"4.4. Statistical Analysis\" paragraph 2", "quote": "Significance of survival curves was computed with the Log-rank test, using the surv_pvalue function of the Survminer R package [54,55], p-values are reported in Table S2."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Uveal melanoma gene expression, and methylation data used in this work is publicly available. TCGA RNA-seq, methylation data is available on http://gdac.broadinstitute.org/ (accessed on 27 September 2023), Affymetrix arrays were previously published on GEO (GSE51880, GSE27831).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37958591", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "Uveal melanoma gene expression, and methylation data used in this work is publicly available. TCGA RNA-seq, methylation data is available on http://gdac.broadinstitute.org/ (accessed on 27 September 2023), Affymetrix arrays were previously published on GEO (GSE51880, GSE27831)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The molecular risk factors of uveal melanoma metastasis are generally acquired independently, with metastatic risk arising from their accumulation rather than from an obligatory sequence.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37958591", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "All other features (6p, 8q, M3, SF3B1 mutation) were present independently from each other."}, {"asset": "source:pmid:37958591", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Several gene expression events that show a non-significant association with outcome when considering single features become significant when analyzing combinations of risk features indicating additive action."}, {"asset": "source:pmid:37958591", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The independence of risk factors is consistent with a random risk model of UM metastasis without an obligatory sequence."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The molecular risk factors of uveal melanoma metastasis are generally acquired independently, with metastatic risk arising from their accumulation rather than from an obligatory sequence.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37958591"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE27831"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE27831"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37958591", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms242115602", "sha256": "sha256:626db7de8d121e11f51af1875af53f2e7e892e22bbf46fd06ed1df6805567c82", "bytes": 49927, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms242115602", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10648765", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE27831", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27831", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27831", "version": null, "note": "Uveal melanoma gene expression, and methylation data used in this work is publicly available. 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We used the NEMO R package [42], selecting k = 4, to perform Data Fusion on the Uveal Melanoma dataset. The relationship between gene expression and mean methylation levels was computed in R, using the Pearson Correlation Coefficient (PCC), associated p-value was computed with the cor.test R function, all values are reported in Table S1. Significance of survival curves was computed with the Log-rank test, using the surv_pvalue function of the Survminer R package [54,55], p-values are reported in Table S2."], "order_basis": "analysis_only", "id": "assay:1"}]}