Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.
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Publication year
2010Source
Histopathology, 56, 1, (2010), pp. 121-32ISSN
Annotation
01 januari 2010
Publication type
Article / Letter to editor
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Organization
Pathology
Anatomy
Donders Centre for Cognitive Neuroimaging
Former Organization
F.C. Donders Centre for Cognitive Neuroimaging
Journal title
Histopathology
Volume
vol. 56
Issue
iss. 1
Page start
p. 121
Page end
p. 32
Subject
130 000 Cognitive Neurology & Memory; 130 030 The schema-consolidation hypothesis; DCN 2: Functional Neurogenomics; ONCOL 3: Translational research; ONCOL 5: Aetiology, screening and detectionAbstract
This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect these cytogenetic alterations in melanocytic tumours are described. In addition, the potential value of more novel techniques such as multiplex ligation-dependent probe amplification is pointed out. This review demonstrates that at present cytogenetics has mainly increased our understanding of the pathogenesis of melanocytic tumours, with an important role for activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the initiation of melanocytic tumours. Mutations in BRAF (in common naevocellular naevi), NRAS (congenital naevi), HRAS (Spitz naevi) and GNAQ (blue naevi) can all cause MAPK activation. All these mutations seem early events in the development of melanocytic tumours, but by themselves are insufficient to cause progression towards melanoma. Additional molecular alterations are implicated in progression towards melanoma, with different genetic alterations in melanomas at different sites and with varying levels of sun exposure. This genetic heterogeneity in distinct types of naevi and melanomas can be used for the development of molecular tests for diagnostic purposes. However, at the moment only few molecular tests have become of diagnostic value and are performed in daily routine practice. This is caused by lack of large prospective studies on the diagnostic value of molecular tests including follow-up, and by the low prevalence of certain molecular alterations. For the future we foresee an increasing role for cytogenetics in the treatment of melanoma patients with the increasing availability of targeted therapy. Potential targets for metastatic melanoma include genes involved in the MAPK pathway, such as BRAF and RAS. More recently, KIT has emerged as a potential target in melanoma patients. These targeted treatments all need careful evaluation, but might be a promising adjunct for treatment of metastatic melanoma patients, in which other therapies have not brought important survival advantages yet.
This item appears in the following Collection(s)
- Academic publications [238441]
- Donders Centre for Cognitive Neuroimaging [3824]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
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