Abstract 3167: Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations.

1) Background Melanoma is a heterogeneous disease and even though consistent genetic patterns among different subtypes have been revealed, clinical trials have failed to significantly improve survival. However, most of the genomic studies do not take into consideration the underlying genomic heterogeneity. In this study, we used genomic profiling of sorted clonal tumor populations in order to investigate the genomic heterogeneity and the clonal evolution in malignant melanoma. 2) Methods Multiple biopsies from melanoma patients were subjected to flow-sorting based on DNA content. The tumor specific marker SOX10 was used as an additional parameter to exclude contribution of normal tissue. Resulting clonal tumor populations were genomically characterized by usage of high resolution aCGH. A TMA was constructed for validation of the findings. 3) Results DNA content based flow sorting of small human melanoma biopsies was successfully implemented and revealed the co-existence of distinct clonal populations (diploid as well as aneuploid) within these samples. The use of the additional marker SOX10 allowed us to uncover and sort pure diploid tumor populations from diploid fractions admixed with normal cells. These findings were confirmed by aCGH. 4) Conclusions Human malignant melanoma is composed of different clonal populations with population-specific genomic aberrations. The use of SOX10 allowed unraveling of pure tumor populations within the diploid peaks, which would have been obscured by the use of DNA content alone. Further genomic analyses of these sorted clonal tumor populations are fundamental for the understanding of the genomic heterogeneity and its potential impact on metastasis and therapy response in malignant melanoma. Citation Format: Thomas Lorber, Tanja Dietsche, Joel Gsponer, Alexander Rufle, Michael Barret, Lukas Sommer, Katharina Glatz, Christian Ruiz, Lukas Bubendorf. Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3167. doi:10.1158/1538-7445.AM2013-3167