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Multiple metastases from cutaneous malignant melanoma patients may display heterogeneous genomic and epigenomic patterns.

Author:
  • Katja Harbst
  • Johan Staaf
  • Anna Måsbäck
  • Håkan Olsson
  • Christian Ingvar
  • Johan Vallon-Christersson
  • Markus Ringnér
  • Åke Borg
  • Göran B Jönsson
Publishing year: 2010
Language: English
Pages: 381-391
Publication/Series: Melanoma Research
Volume: 20
Issue: 5
Document type: Journal article
Publisher: Lippincott Williams & Wilkins

Abstract english

Disseminated melanoma is an aggressive disease with fatal outcome. Better understanding of the underlying biology is needed to find effective treatment. We applied microarray-based comparative genomic hybridization, gene expression and CpG island methylation analysis of primary tumors and multiple metastases from five melanoma patients with the aim of analyzing the molecular patterns of melanoma progression. Epigenetic profiling showed that the multiple metastases after a single primary melanoma share similar methylation patterns for many genes, although differences in methylation between the lesions were evident for several genes, example, PTEN, TFAP2C, and RARB. In addition, DNA copy number and global gene expression profiles of tumors from individual patients were highly similar, confirming common origin of metastases. Some of the identified genomic aberrations, for example, gain of chromosome 6p and loss of chromosomes 6q and 10, persisted during progression, indicating early changes highly important for melanoma development. Homozygous deletions at 3p26.1 and 6q23.2-q23.3 appeared in two consecutive metastases originating from the same primary tumor, respectively, in a mutually exclusive manner that provides evidence for two genetically different subclones. However, in another case, the similarity of the copy number aberrations in subsequent metastatic lesions suggests sequential metastatic development through the clonal evolution. These data are further corroborated by a switch in CDH1 and CDH2 expression between metastases from the same patient. In conclusion, our results provide evidence for different models of metastatic progression in melanoma.

Keywords

  • Surgery
  • Cancer and Oncology

Other

Published
  • CREATE Health
  • ISSN: 0960-8931
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90