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

Harbst, Katja LU ; Staaf, Johan LU ; Måsbäck, Anna; Olsson, Håkan LU ; Ingvar, Christian LU ; Vallon-Christersson, Johan LU ; Ringnér, Markus LU ; Borg, Åke LU and Jönsson, Göran B LU (2010) In Melanoma Research 20(5). p.381-391
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Melanoma Research
volume
20
issue
5
pages
381 - 391
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000281615000003
  • pmid:20848731
  • scopus:77957553866
ISSN
0960-8931
DOI
10.1097/CMR.0b013e32833b7c7c
project
CREATE Health
language
English
LU publication?
yes
id
85070a4e-c24b-49d0-a3f5-f0b4ad2c63a3 (old id 1688105)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20848731?dopt=Abstract
date added to LUP
2010-10-05 10:29:17
date last changed
2018-05-29 10:13:33
@article{85070a4e-c24b-49d0-a3f5-f0b4ad2c63a3,
  abstract     = {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.},
  author       = {Harbst, Katja and Staaf, Johan and Måsbäck, Anna and Olsson, Håkan and Ingvar, Christian and Vallon-Christersson, Johan and Ringnér, Markus and Borg, Åke and Jönsson, Göran B},
  issn         = {0960-8931},
  language     = {eng},
  number       = {5},
  pages        = {381--391},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Melanoma Research},
  title        = {Multiple metastases from cutaneous malignant melanoma patients may display heterogeneous genomic and epigenomic patterns.},
  url          = {http://dx.doi.org/10.1097/CMR.0b013e32833b7c7c},
  volume       = {20},
  year         = {2010},
}