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

Terrence M. Katona, Timothy D. Jones, Mingsheng Wang, John N. Eble, Steven D. Billings, Liang Cheng

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2007

Keywords

  • Clonality
  • Cutaneous neoplasia
  • Loss of heterozygosity
  • Lymph node metastasis
  • Malignant melanoma
  • Progression
  • Skin
  • X chromosome inactivation

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

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