Genetically heterogeneous and clonally unrelated metastases may arise in patients with cutaneous melanoma

Am J Surg Pathol. 2007 Jul;31(7):1029-37. doi: 10.1097/PAS.0b013e31802b3488.


Melanoma of the skin frequently metastasizes to multiple regional lymph nodes and to distant sites. It is uncertain whether all metastases originate from the same tumor clone or whether the genetic heterogeneity of the primary tumor is reflected in the multiple metastases. A total of 73 archival, formalin-fixed, paraffin-embedded, melanoma lesions, including 13 primary tumors and 60 metastases, were studied from 13 patients each having 2 or more metastatic tumors. Genomic DNA samples were prepared from tissue sections using laser-assisted microdissection. We find that the majority of melanoma metastases share a common clonal origin with the matched primary tumor. However, significant genetic divergence occurs frequently during the clonal evolution of metastatic melanoma. In addition, using X-chromosome inactivation analysis, we find that, in some cases, multiple coexisting metastases seem to be derived from different, genetically unrelated tumor clones, implying that some primary tumors may arise from more than a single transformed melanocyte.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, X
  • Clone Cells*
  • DNA, Neoplasm / analysis
  • Female
  • Humans
  • Loss of Heterozygosity
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Melanoma / genetics
  • Melanoma / secondary*
  • Melanoma / surgery
  • Microdissection
  • Middle Aged
  • Sentinel Lymph Node Biopsy
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • X Chromosome Inactivation


  • DNA, Neoplasm