Academic Journal
Copy Number Analysis in Congenital Nevi: Concordance and Diagnostic Limitations of aCGH, sWGS, and Methylation Sequencing.
| Τίτλος: | Copy Number Analysis in Congenital Nevi: Concordance and Diagnostic Limitations of aCGH, sWGS, and Methylation Sequencing. |
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| Συγγραφείς: | Karelin A; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany., Brecht IB; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany., Pogoda M; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany.; NGS Competence Center, Tübingen, Germany., Demidov G; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany., Abele M; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany., Schneider DT; Clinic of Pediatrics, Klinikum Dortmund, University Witten/Herdecke, Dortmund, Germany., Aldea D; Aix Marseille University, INSERM, Marseille Medical Genetics, Marseille, France., Etchevers HC; Aix Marseille University, INSERM, Marseille Medical Genetics, Marseille, France., Puig S; Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Institut de Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.; Centro de Investigación BIomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain., Hahn M; Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany., Schroeder C; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany., Forchhammer S; Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany. |
| Συλλογικό Έργο: | MELCAYA consortium |
| Πηγή: | Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2026 Jul; Vol. 39 (4), pp. e70097. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Blackwell Munksgaard Country of Publication: England NLM ID: 101318927 Publication Model: Print Cited Medium: Internet ISSN: 1755-148X (Electronic) Linking ISSN: 17551471 NLM ISO Abbreviation: Pigment Cell Melanoma Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford : Blackwell Munksgaard |
| Ιατρικοί όροι (MeSH): | DNA Methylation*/genetics , DNA Copy Number Variations*/genetics , Comparative Genomic Hybridization*/methods , Nevus, Pigmented*/genetics , Nevus, Pigmented*/diagnosis , Nevus, Pigmented*/congenital , Skin Neoplasms*/genetics , Skin Neoplasms*/diagnosis , Whole Genome Sequencing*, Humans ; Female ; Male ; Child, Preschool ; Infant ; Child |
| Περίληψη: | Distinguishing benign proliferative nodules (PNs) from melanoma arising within congenital melanocytic nevi remains a major diagnostic challenge. Copy number alteration (CNA) analysis is widely used to support classification, but current criteria were developed using array comparative genomic hybridization (aCGH). The performance of alternative platforms such as shallow whole-genome sequencing (sWGS) and methylation sequencing is poorly defined in this context. The objective of this study is to compare CNA profiles obtained from aCGH, sWGS, and methylation sequencing in atypical nodules arising within congenital nevi, and to explore their clinical context based on available follow-up data. Sixteen samples from 14 patients were retrospectively analyzed using all three platforms. CNAs were cataloged, concordance across methods was quantified using the Jaccard index, and molecular classifications were compared. Clinical follow-up was reviewed to provide clinical context. aCGH detected 39 CNAs, sWGS 60, and methylation sequencing 66. Concordance was highest between sWGS and methylation (mean Jaccard 0.67), followed by aCGH versus sWGS (0.64) and aCGH versus methylation (0.49). Cases with high aneuploidy demonstrated strong cross-platform agreement, whereas low-burden lesions exhibited greater variability between methods. Divergent molecular classifications were observed in six cases. While all methods reliably detect broad chromosomal changes, sWGS and methylation sequencing identify many additional focal CNAs that may not align with CGH-based diagnostic criteria. These findings highlight the need for platform-adapted thresholds and validation in larger outcome-linked cohorts. (© 2026 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.) |
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| Grant Information: | Grant Agreement No 101096667 European Commission; Project-ID 286/2020B01-428994620 Deutsche Forschungsgemeinschaft |
| Contributed Indexing: | Keywords: CGH; DNA methylation sequencing; congenital melanocytic nevus; copy number alteration; pediatric melanoma; proliferative nodule; shallow whole‐genome sequencing |
| Entry Date(s): | Date Created: 20260604 Date Completed: 20260611 Latest Revision: 20260611 |
| Update Code: | 20260611 |
| DOI: | 10.1111/pcmr.70097 |
| PMID: | 42237736 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1755-148X |
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| DOI: | 10.1111/pcmr.70097 |