Identification of genetic disparity between primary and metastatic melanoma in human patients

Genes Chromosomes Cancer. 2011 Sep;50(9):680-8. doi: 10.1002/gcc.20890. Epub 2011 May 16.


It is commonly accepted that cancer cell progression is accompanied by accumulation of genetic changes. Here we searched for copy number variations in melanoma and asked whether homozygous losses always cumulate during tumor cell progression. Therefore we investigated either melanoma cell lines or tissue derived from the primary lesion and from the lymph node metastasis of the same individual patient. In vitro studies of melanoma cell lines revealed high migratory and anchorage independent growth of metastasis-derived cells. Surprisingly, whole genome DNA analysis of a primum-derived cell line revealed a total of 10 homozygous losses, whereas the matched metastasis-derived cell line only shared five of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Additionally, we screened matched pairs of patient-derived melanoma primum and metastasis samples and we could also identify a case with homozygous deletions exclusively present in the primary lesion. Therefore, we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but also from metastatic melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Shape
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • DNA Copy Number Variations
  • Female
  • Genome-Wide Association Study
  • Humans
  • Lymphatic Metastasis
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • X Chromosome / genetics