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Copy Number Analysis in Congenital Nevi: Concordance and Diagnostic Limitations of aCGH, sWGS, and Methylation Sequencing.

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Τίτλος: Copy Number Analysis in Congenital Nevi: Concordance and Diagnostic Limitations of aCGH, sWGS, and Methylation Sequencing.
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.)
References: Alomari, A. K., J. R. Miedema, M. D. Carter, et al. 2020. “DNA Copy Number Changes Correlate With Clinical Behavior in Melanocytic Neoplasms: Proposal of an Algorithmic Approach.” Modern Pathology 33, no. 7: 1307–1317.
Ardakani, N. M., C. Thomas, C. Robinson, et al. 2017. “Detection of Copy Number Variations in Melanocytic Lesions Utilising Array Based Comparative Genomic Hybridisation.” Pathology 49, no. 3: 285–291.
Bastian, B. C., J. Xiong, I. J. Frieden, et al. 2002. “Genetic Changes in Neoplasms Arising in Congenital Melanocytic Nevi: Differences Between Nodular Proliferations and Melanomas.” American Journal of Pathology 161, no. 4: 1163–1169.
Bauer, J., and B. C. Bastian. 2006. “Distinguishing Melanocytic Nevi From Melanoma by DNA Copy Number Changes: Comparative Genomic Hybridization as a Research and Diagnostic Tool.” Dermatologic Therapy 19, no. 1: 40–49.
Coutelier, M., M. Holtgrewe, M. Jäger, et al. 2022. “Combining Callers Improves the Detection of Copy Number Variants From Whole‐Genome Sequencing.” European Journal of Human Genetics 30, no. 2: 178–186.
Demidov, G., and S. Ossowski. 2019. “ClinCNV: Novel Method for Allele‐Specific Somatic Copy‐Number Alterations Detection.” BioRxiv, 837971.
Ferrari, A., I. B. Brecht, G. Gatta, et al. 2019. “Defining and Listing Very Rare Cancers of Paediatric Age: Consensus of the Joint Action on Rare Cancers in Cooperation With the European Cooperative Study Group for Pediatric Rare Tumors.” European Journal of Cancer 110: 120–126.
Geiersbach, K. B., T. J. Gliem, S. M. Jenkins, et al. 2022. “Single‐Nucleotide Polymorphism Array for Histologically Ambiguous Melanocytic Tumors.” Journal of Molecular Diagnostics 24, no. 11: 1160–1170.
Hawryluk, E. B., D. Moustafa, D. Bartenstein, et al. 2020. “A Retrospective Multicenter Study of Fatal Pediatric Melanoma.” Journal of the American Academy of Dermatology 83, no. 5: 1274–1281.
Hayes, J., A. Tzika, H. Thygesen, et al. 2013. “Diagnosis of Copy Number Variation by Illumina Next Generation Sequencing Is Comparable in Performance to Oligonucleotide Array Comparative Genomic Hybridisation.” Genomics 102, no. 3: 174–181.
Krueger, F., and S. R. Andrews. 2011. “Bismark: A Flexible Aligner and Methylation Caller for Bisulfite‐Seq Applications.” Bioinformatics 27, no. 11: 1571–1572.
Liu, Y., S. Hao, X. Guo, et al. 2023. “Accuracy and Depth Evaluation of Clinical Low Pass Genome Sequencing in the Detection of Mosaic Aneuploidies and CNVs.” BMC Medical Genomics 16, no. 1: 294.
McMullan, P., and J. M. Grant‐Kels. 2025. “Childhood and Adolescent Melanoma: An Update.” Clinics in Dermatology 43, no. 1: 16–23.
Merkel, E. A., L. S. Mohan, K. Shi, E. Panah, B. Zhang, and P. Gerami. 2019. “Paediatric Melanoma: Clinical Update, Genetic Basis, and Advances in Diagnosis.” Lancet Child & Adolescent Health 3, no. 9: 646–654.
Miele, E., S. Rossi, A. Stracuzzi, et al. 2025. “Epigenomic Characterization and Therapeutic Challenges of Melanoma Arising in Giant Nevi in Pediatric Patients.” Discover Oncology 16, no. 1: 2164.
North, J. P., S. S. Vemula, and B. C. Bastian. 2013. “Chromosomal Copy Number Analysis in Melanoma Diagnostics.” In Molecular Diagnostics for Melanoma: Methods and Protocols, 199–226. Springer.
Pampena, R., V. Piccolo, M. Muscianese, et al. 2023. “Melanoma in Children: A Systematic Review and Individual Patient Meta‐Analysis.” Journal of the European Academy of Dermatology and Venereology 37: 1758–1776.
Pappo, A. S., V. McPherson, H. Pan, et al. 2021. “A Prospective, Comprehensive Registry That Integrates the Molecular Analysis of Pediatric and Adolescent Melanocytic Lesions.” Cancer 127, no. 20: 3825–3831.
Pavlova, O., S. Fraitag, and D. Hohl. 2016. “5‐Hydroxymethylcytosine Expression in Proliferative Nodules Arising Within Congenital Nevi Allows Differentiation From Malignant Melanoma.” Journal of Investigative Dermatology 136, no. 12: 2453–2461.
Phadke, P. A., D. Rakheja, L. P. Le, et al. 2011. “Proliferative Nodules Arising Within Congenital Melanocytic Nevi: A Histologic, Immunohistochemical, and Molecular Analyses of 43 Cases.” American Journal of Surgical Pathology 35, no. 5: 656–669.
Robberecht, C., J.‐P. Fryns, and J. R. Vermeesch. 2010. “Piecing Together the Problems in Diagnosing Low‐Level Chromosomal Mosaicism.” Genome Medicine 2, no. 7: 47.
Rossi, S., S. Barresi, I. Giovannoni, et al. 2026. “Melanomas and Mesenchymal Tumors Arising in Giant Congenital Melanocytic Nevi: Clinico‐Pathological and Molecular Characterization of a Case Series.” Pigment Cell & Melanoma Research 39, no. 1: e70071.
Scheinin, I., D. Sie, H. Bengtsson, et al. 2014. “DNA Copy Number Analysis of Fresh and Formalin‐Fixed Specimens by Shallow Whole‐Genome Sequencing With Identification and Exclusion of Problematic Regions in the Genome Assembly.” Genome Research 24, no. 12: 2022–2032.
Tran, Q. T., S. Jia, M. Z. Alom, et al. 2025. “Validation of Target‐Enriched Enzymatic Methylation Sequencing for Brain Tumor Classification From Formalin‐Fixed Paraffin Embedded‐Derived DNA.” Brain Pathology 35, no. 5: e70000.
Van der Linden, M., L. Raman, A. Vander Trappen, et al. 2020. “Detection of Copy Number Alterations by Shallow Whole‐Genome Sequencing of Formalin‐Fixed, Paraffin‐Embedded Tumor Tissue.” Archives of Pathology & Laboratory Medicine 144, no. 8: 974–981.
Vasimuddin, M., S. Misra, H. Li, and S. Aluru. 2019. “Efficient Architecture‐Aware Acceleration of BWA‐MEM for Multicore Systems.” 2019 IEEE International Parallel and Distributed Processing Symposium (IPDPS).
Vergier, B., E. Laharanne, M. Prochazkova‐Carlotti, et al. 2016. “Proliferative Nodules vs. Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood.” JAMA Dermatology 152, no. 10: 1147–1151.
Wang, J., Y. Lan, H.‐Y. Qi, et al. 2025. “Comparison of Fluorescence in Situ Hybridization, Next‐Generation Sequencing, and DNA Methylation Microarray for Copy Number Variation Assessment in Gliomas.” Laboratory Investigation 105, no. 7: 104168.
Wang, N., Z.‐Y. Tao, T. Wu, et al. 2025. “Benchmarking Copy Number Variation Detection With Low‐Coverage Whole‐Genome Sequencing.” Briefings in Bioinformatics 26, no. 5: bbaf514.
Yélamos, O., N. C. Arva, R. Obregon, et al. 2015. “A Comparative Study of Proliferative Nodules and Lethal Melanomas in Congenital Nevi From Children.” American Journal of Surgical Pathology 39, no. 3: 405–415.
Yousif, R., C. Boull, P. Gerami, B. Nardone, K. L. Vivar, and W. Liszewski. 2021. “The Demographics and Trends in Pediatric Melanoma in the United States: An Analysis of the National Cancer Database.” Pediatric Dermatology 38, no. 5: 1191–1197.
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
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  Label: Title
  Group: Ti
  Data: Copy Number Analysis in Congenital Nevi: Concordance and Diagnostic Limitations of aCGH, sWGS, and Methylation Sequencing.
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  Data: <searchLink fieldCode="AU" term="%22Karelin+A%22">Karelin A</searchLink>; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Brecht+IB%22">Brecht IB</searchLink>; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Pogoda+M%22">Pogoda M</searchLink>; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany.; NGS Competence Center, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Demidov+G%22">Demidov G</searchLink>; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Abele+M%22">Abele M</searchLink>; Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Schneider+DT%22">Schneider DT</searchLink>; Clinic of Pediatrics, Klinikum Dortmund, University Witten/Herdecke, Dortmund, Germany.<br /><searchLink fieldCode="AU" term="%22Aldea+D%22">Aldea D</searchLink>; Aix Marseille University, INSERM, Marseille Medical Genetics, Marseille, France.<br /><searchLink fieldCode="AU" term="%22Etchevers+HC%22">Etchevers HC</searchLink>; Aix Marseille University, INSERM, Marseille Medical Genetics, Marseille, France.<br /><searchLink fieldCode="AU" term="%22Puig+S%22">Puig S</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Hahn+M%22">Hahn M</searchLink>; Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Schroeder+C%22">Schroeder C</searchLink>; Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tübingen, Tübingen, Germany.<br /><searchLink fieldCode="AU" term="%22Forchhammer+S%22">Forchhammer S</searchLink>; Department of Dermatology, Eberhard Karls University of Tübingen, Tübingen, Germany.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Blackwell+Munksgaard%22">Blackwell Munksgaard </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101318927 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1755-148X (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2217551471%22">17551471 </searchLink><i>NLM ISO Abbreviation: </i>Pigment Cell Melanoma Res <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Oxford : Blackwell Munksgaard
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  Data: <searchLink fieldCode="MM" term="%22DNA+Methylation%22">DNA Methylation*</searchLink>/<searchLink fieldCode="MM" term="%22DNA+Methylation+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22DNA+Copy+Number+Variations%22">DNA Copy Number Variations*</searchLink>/<searchLink fieldCode="MM" term="%22DNA+Copy+Number+Variations+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Comparative+Genomic+Hybridization%22">Comparative Genomic Hybridization*</searchLink>/<searchLink fieldCode="MM" term="%22Comparative+Genomic+Hybridization+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented%22">Nevus, Pigmented*</searchLink>/<searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented%22">Nevus, Pigmented*</searchLink>/<searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented+diagnosis%22">diagnosis</searchLink> <br /><searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented%22">Nevus, Pigmented*</searchLink>/<searchLink fieldCode="MM" term="%22Nevus%2C+Pigmented+congenital%22">congenital</searchLink> <br /><searchLink fieldCode="MM" term="%22Skin+Neoplasms%22">Skin Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Skin+Neoplasms+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Skin+Neoplasms%22">Skin Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Skin+Neoplasms+diagnosis%22">diagnosis</searchLink> <br /><searchLink fieldCode="MM" term="%22Whole+Genome+Sequencing%22">Whole Genome Sequencing*</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Child%2C+Preschool%22">Child, Preschool</searchLink> ; <searchLink fieldCode="MH" term="%22Infant%22">Infant</searchLink> ; <searchLink fieldCode="MH" term="%22Child%22">Child</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.<br /> (© 2026 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Alomari, A. K., J. R. Miedema, M. D. Carter, et al. 2020. “DNA Copy Number Changes Correlate With Clinical Behavior in Melanocytic Neoplasms: Proposal of an Algorithmic Approach.” Modern Pathology 33, no. 7: 1307–1317.<br />Ardakani, N. M., C. Thomas, C. Robinson, et al. 2017. “Detection of Copy Number Variations in Melanocytic Lesions Utilising Array Based Comparative Genomic Hybridisation.” Pathology 49, no. 3: 285–291.<br />Bastian, B. C., J. Xiong, I. J. Frieden, et al. 2002. “Genetic Changes in Neoplasms Arising in Congenital Melanocytic Nevi: Differences Between Nodular Proliferations and Melanomas.” American Journal of Pathology 161, no. 4: 1163–1169.<br />Bauer, J., and B. C. Bastian. 2006. “Distinguishing Melanocytic Nevi From Melanoma by DNA Copy Number Changes: Comparative Genomic Hybridization as a Research and Diagnostic Tool.” Dermatologic Therapy 19, no. 1: 40–49.<br />Coutelier, M., M. Holtgrewe, M. Jäger, et al. 2022. “Combining Callers Improves the Detection of Copy Number Variants From Whole‐Genome Sequencing.” European Journal of Human Genetics 30, no. 2: 178–186.<br />Demidov, G., and S. Ossowski. 2019. “ClinCNV: Novel Method for Allele‐Specific Somatic Copy‐Number Alterations Detection.” BioRxiv, 837971.<br />Ferrari, A., I. B. Brecht, G. Gatta, et al. 2019. “Defining and Listing Very Rare Cancers of Paediatric Age: Consensus of the Joint Action on Rare Cancers in Cooperation With the European Cooperative Study Group for Pediatric Rare Tumors.” European Journal of Cancer 110: 120–126.<br />Geiersbach, K. B., T. J. Gliem, S. M. Jenkins, et al. 2022. “Single‐Nucleotide Polymorphism Array for Histologically Ambiguous Melanocytic Tumors.” Journal of Molecular Diagnostics 24, no. 11: 1160–1170.<br />Hawryluk, E. B., D. Moustafa, D. Bartenstein, et al. 2020. “A Retrospective Multicenter Study of Fatal Pediatric Melanoma.” Journal of the American Academy of Dermatology 83, no. 5: 1274–1281.<br />Hayes, J., A. Tzika, H. Thygesen, et al. 2013. “Diagnosis of Copy Number Variation by Illumina Next Generation Sequencing Is Comparable in Performance to Oligonucleotide Array Comparative Genomic Hybridisation.” Genomics 102, no. 3: 174–181.<br />Krueger, F., and S. R. Andrews. 2011. “Bismark: A Flexible Aligner and Methylation Caller for Bisulfite‐Seq Applications.” Bioinformatics 27, no. 11: 1571–1572.<br />Liu, Y., S. Hao, X. Guo, et al. 2023. “Accuracy and Depth Evaluation of Clinical Low Pass Genome Sequencing in the Detection of Mosaic Aneuploidies and CNVs.” BMC Medical Genomics 16, no. 1: 294.<br />McMullan, P., and J. M. Grant‐Kels. 2025. “Childhood and Adolescent Melanoma: An Update.” Clinics in Dermatology 43, no. 1: 16–23.<br />Merkel, E. A., L. S. Mohan, K. Shi, E. Panah, B. Zhang, and P. Gerami. 2019. “Paediatric Melanoma: Clinical Update, Genetic Basis, and Advances in Diagnosis.” Lancet Child & Adolescent Health 3, no. 9: 646–654.<br />Miele, E., S. Rossi, A. Stracuzzi, et al. 2025. “Epigenomic Characterization and Therapeutic Challenges of Melanoma Arising in Giant Nevi in Pediatric Patients.” Discover Oncology 16, no. 1: 2164.<br />North, J. P., S. S. Vemula, and B. C. Bastian. 2013. “Chromosomal Copy Number Analysis in Melanoma Diagnostics.” In Molecular Diagnostics for Melanoma: Methods and Protocols, 199–226. Springer.<br />Pampena, R., V. Piccolo, M. Muscianese, et al. 2023. “Melanoma in Children: A Systematic Review and Individual Patient Meta‐Analysis.” Journal of the European Academy of Dermatology and Venereology 37: 1758–1776.<br />Pappo, A. S., V. McPherson, H. Pan, et al. 2021. “A Prospective, Comprehensive Registry That Integrates the Molecular Analysis of Pediatric and Adolescent Melanocytic Lesions.” Cancer 127, no. 20: 3825–3831.<br />Pavlova, O., S. Fraitag, and D. Hohl. 2016. “5‐Hydroxymethylcytosine Expression in Proliferative Nodules Arising Within Congenital Nevi Allows Differentiation From Malignant Melanoma.” Journal of Investigative Dermatology 136, no. 12: 2453–2461.<br />Phadke, P. A., D. Rakheja, L. P. Le, et al. 2011. “Proliferative Nodules Arising Within Congenital Melanocytic Nevi: A Histologic, Immunohistochemical, and Molecular Analyses of 43 Cases.” American Journal of Surgical Pathology 35, no. 5: 656–669.<br />Robberecht, C., J.‐P. Fryns, and J. R. Vermeesch. 2010. “Piecing Together the Problems in Diagnosing Low‐Level Chromosomal Mosaicism.” Genome Medicine 2, no. 7: 47.<br />Rossi, S., S. Barresi, I. Giovannoni, et al. 2026. “Melanomas and Mesenchymal Tumors Arising in Giant Congenital Melanocytic Nevi: Clinico‐Pathological and Molecular Characterization of a Case Series.” Pigment Cell & Melanoma Research 39, no. 1: e70071.<br />Scheinin, I., D. Sie, H. Bengtsson, et al. 2014. “DNA Copy Number Analysis of Fresh and Formalin‐Fixed Specimens by Shallow Whole‐Genome Sequencing With Identification and Exclusion of Problematic Regions in the Genome Assembly.” Genome Research 24, no. 12: 2022–2032.<br />Tran, Q. T., S. Jia, M. Z. Alom, et al. 2025. “Validation of Target‐Enriched Enzymatic Methylation Sequencing for Brain Tumor Classification From Formalin‐Fixed Paraffin Embedded‐Derived DNA.” Brain Pathology 35, no. 5: e70000.<br />Van der Linden, M., L. Raman, A. 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  Data: <i>Keywords: </i>CGH; DNA methylation sequencing; congenital melanocytic nevus; copy number alteration; pediatric melanoma; proliferative nodule; shallow whole‐genome sequencing
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        Text: English
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      – SubjectFull: Child
        Type: general
      – SubjectFull: DNA Methylation genetics
        Type: general
      – SubjectFull: DNA Copy Number Variations genetics
        Type: general
      – SubjectFull: Comparative Genomic Hybridization methods
        Type: general
      – SubjectFull: Nevus, Pigmented genetics
        Type: general
      – SubjectFull: Nevus, Pigmented diagnosis
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      – SubjectFull: Nevus, Pigmented congenital
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      – SubjectFull: Skin Neoplasms diagnosis
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      – SubjectFull: Whole Genome Sequencing
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              Text: 2026 Jul
              Type: published
              Y: 2026
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