Phylogenetic Analyses Reveal Complex Patterns of Melanoma Metastasis

Subpopulations of cells in a primary melanoma can disseminate and establish metastases. Still, the precise ancestral relationship between primary tumors and their metastases is not well understood. Using whole-exome sequencing (for discovery) and targeted sequencing (for validation), we analyzed mutation patterns of primary melanomas and two or more metastases in each of 8 patients to determine their phylogenetic relationships, profiling a total of 31 total tumors. The resulting data show that in 6 of 8 cases, genetically unique cell populations in the primary metastasized in parallel to distinct anatomic sites, rather than sequentially. These data also indicate that individual metastases were sometimes founded by multiple cell populations of the primary that were genetically distinct.]]>
Tumor samples were obtained from 1) the Melanoma Institute Australia (MIA) Biospecimen Bank, a prospective collection of fresh-frozen tumors accrued with informed consent and IRB approval since 1996 through MIA (formerly the Sydney Melanoma Unit); and 2) the Tumor Procurement Service of Memorial Sloan-Kettering Cancer Center (MSKCC), a biospecimen collection of fresh-frozen tumors acquired and managed in accordance with requirements stipulated by the Institutional Review Board and the Human Biospecimen Utilization Committee of MSKCC. Tumors were included from patients for whom primary melanomas and two or more metastases were available. No samples were excluded during the course of the study. There were no additional exclusion criteria.]]>