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Open Access Highly Accessed Research article

Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma

Jared J Gartner1, Sean Davis2, Xiaomu Wei1, Jimmy C Lin3, Niraj S Trivedi7, Jamie K Teer4, NISC Comparative Sequencing Program5, Paul S Meltzer2, Steven A Rosenberg6 and Yardena Samuels1*

Author Affiliations

1 The Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

2 The Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

3 Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

4 Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

5 NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

6 The Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

7 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

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BMC Genomics 2012, 13:505  doi:10.1186/1471-2164-13-505

Published: 24 September 2012

Abstract

Background

Metastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs.

Results

Using stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined.

Conclusions

These data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.