The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Summary, in 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.

Department/s

  • Breastcancer-genetics
  • Surgery (Lund)
  • EpiHealth: Epidemiology for Health
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2010

Language

English

Pages

381-391

Publication/Series

Melanoma Research

Volume

20

Issue

5

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Surgery
  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0960-8931