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.