Comparison of mutation profiles in primary melanomas and corresponding nodal naevi using next-generation sequencing.
Journal
Clinical and experimental dermatology
ISSN: 1365-2230
Titre abrégé: Clin Exp Dermatol
Pays: England
ID NLM: 7606847
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
accepted:
27
09
2021
pubmed:
1
10
2021
medline:
5
3
2022
entrez:
30
9
2021
Statut:
ppublish
Résumé
Nodal naevi (NN) represent aggregates of melanocytes within peripheral lymph nodes. NN are relatively often found in patients with malignant melanoma (MM), and may mimic metastatic disease. To study mutation profiles in MM and NN to find out whether NN descend from a primary MM. Next-generation sequencing was performed on formalin-fixed paraffin-embedded tissue of 26 pairs of primary MM and corresponding NN detected by sentinel lymph node biopsy, and 29 MM-characteristic genes were investigated. In this study, 90% of mutations were detected exclusively in either MM or NN, but not both, in the same patient; the percentage of identical NN and MM mutations in the same individual was only 10%. The most frequently discovered shared mutations were a C>G substitution in the CDKN2A gene and in-frame deletion in ARID1A. Oncogenic driver mutations were frequently observed in MM but only rarely in NN. About three-quarters of mutations in both MM and NN were characterized by C>T or G>A substitutions. The detected rate of ultraviolet (UV)-related C>T base changes was comparably high in both primary MM (35%) and NN (32%). Based on our data, it seems that NN descend from previously UV-exposed BRAF wildtype cutaneous melanocytes, rather than from primary MM or arrested progenitor cells.
Sections du résumé
BACKGROUND
BACKGROUND
Nodal naevi (NN) represent aggregates of melanocytes within peripheral lymph nodes. NN are relatively often found in patients with malignant melanoma (MM), and may mimic metastatic disease.
AIM
OBJECTIVE
To study mutation profiles in MM and NN to find out whether NN descend from a primary MM.
METHODS
METHODS
Next-generation sequencing was performed on formalin-fixed paraffin-embedded tissue of 26 pairs of primary MM and corresponding NN detected by sentinel lymph node biopsy, and 29 MM-characteristic genes were investigated.
RESULTS
RESULTS
In this study, 90% of mutations were detected exclusively in either MM or NN, but not both, in the same patient; the percentage of identical NN and MM mutations in the same individual was only 10%. The most frequently discovered shared mutations were a C>G substitution in the CDKN2A gene and in-frame deletion in ARID1A. Oncogenic driver mutations were frequently observed in MM but only rarely in NN. About three-quarters of mutations in both MM and NN were characterized by C>T or G>A substitutions. The detected rate of ultraviolet (UV)-related C>T base changes was comparably high in both primary MM (35%) and NN (32%).
CONCLUSIONS
CONCLUSIONS
Based on our data, it seems that NN descend from previously UV-exposed BRAF wildtype cutaneous melanocytes, rather than from primary MM or arrested progenitor cells.
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
373-380Informations de copyright
© 2021 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
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