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Molekulargenetische Analyse bei der Diagnose melanozytärer Tumoren

DNA copy number changes in the diagnosis of melanocytic tumors

  • Schwerpunkt: Melanozytäre Tumoren
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Zusammenfassung

Die Krebsentstehung geht bei vielen Tumoren mit einem Verlust der Kontrolle über die genomische Stabilität einher und resultiert in einem veränderten und durch Selektion bestimmten Genom der Krebszellen. Die komparative genomische Hybridisierung (CGH) ist eine Methode, mit der das Genom von Tumorzellen auf klonale chromosomale Aberrationen untersucht werden kann. Mittels CGH wurde gezeigt, dass sich Melanome von melanozytären Nävi durch häufige chromosomale Aberrationen unterscheiden. Die CGH-Analyse benigner melanozytärer Tumoren zeigt typischerweise keine chromosomalen Veränderungen, während man bei der überwiegenden Anzahl der Melanome Zugewinne und Verluste von bestimmten Chromosomen findet. Eine Ausnahme bilden Spitz-Nävi, bei denen etwa 20% zusätzliche Kopien von Chromosom 11p aufweisen. Diese Aberrationen werden bei Melanomen nicht beobachtet. Diese deutlichen Unterschiede der Aberrationsmuster stellen ein wichtiges Hilfsmittel für die Diagnose histologisch nicht eindeutig klassifizierbarer melanozytärer Tumoren dar. Darüber hinaus konnte mittels CGH und Mutationsanalyse auch gezeigt werden, dass Melanome keine einheitliche Erkrankung, sondern eine Gruppe von genetisch verschiedenen Tumoren sind. Derzeit untersucht eine Studie die Korrelation der chromosomalen Veränderungen bei diagnostisch unklaren melanozytären Tumoren mit dem Erkrankungsverlauf der Patienten.

Abstract

In the case of many tumors, the development of cancer is associated with a loss of control over genomic integrity, resulting in alterations, determined by selection, of the genome of the cancer cells. Comparative genomic hybridization (CGH) is a method that can be used to assess the entire genome of tumor cells for the presence of changes in DNA copy number. CGH analysis has revealed that melanomas differ from melanocytic nevi in the presence of frequent chromosomal aberrations. CGH analysis of benign melanocytic tumors typically shows no clonally expanded chromosomal aberrations, while in the vast majority of melanomas gains and losses of particular chromosomes are found. As an exception, Spitz nevi show an increased copy number of chromosome 11p in about 20% of cases, something not found in melanoma. These marked differences between the aberration patterns of melanomas and melanocytic nevi can be exploited during differential diagnosis of melanocytic tumors in which histopathologic assessment yields equivocal results. In addition, it has also been shown with the aid of CGH and mutation analysis that melanomas are not a homogenous disease, but rather a group of genetically different tumors. A study checking for correlations between the chromosomal alterations in melanocytic tumors not classified at diagnosis and the course of illness in patients is currently under way.

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Authors and Affiliations

  1. Departments of Dermatology and Pathology and Comprehensive Cancer Center, University of California, Box 0808, San Francisco, CA 94143–0808, USA

    J. Bauer &  B.C. Bastian

  2. Universitäts-Hautklinik, Eberhard-Karls-Universität, Tübingen, Deutschland

    J. Bauer

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  2. B.C. Bastian
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Bauer, J., Bastian, B. Molekulargenetische Analyse bei der Diagnose melanozytärer Tumoren. Pathologe 28, 464–473 (2007). https://doi.org/10.1007/s00292-007-0944-4

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