The goal of this Core is to provide the analytical tools and statistical and computational expertise needed to design and analyze the high throughput experiments and data generated by the Projects and Cores of this POI. Additionally, this Core will integrate the data resulting from the Project with external cancer genome data such as that generated by The Cancer Genome Atlas (TCGA) project, in order to elucidate the mechanism(s) of drug resistance.
The Specific Aims of Core 3 are (1) to perform genomic characterization of human and mouse cancer genomes and integrating these data to identify events that cause resistance;(2) Analyze the shRNA and drug response data to identify dependencies in pre-treatment and relapsed cells;(3) Integrate data from this P01 with comprehensive genomic data generated by The Cancer Genome Atlas (TCGA) project to increase statistical power. At the end of the funded period, integrative analysis of all data produced within this P01 and external data will yield a clear set of hypotheses regarding candidate genes, pathways and drugs that are involved in and can affect the development of drug resistance in BRAF-mutant melanoma.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Massachusetts General Hospital
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Roider, Elisabeth M; Fisher, David E (2014) The impact of MITF on melanoma development: news from bench and bedside. J Invest Dermatol 134:16-7
Konieczkowski, David J; Johannessen, Cory M; Abudayyeh, Omar et al. (2014) A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4:816-27
Van Allen, Eliezer M; Wagle, Nikhil; Sucker, Antje et al. (2014) The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 4:94-109
Lo, Jennifer A; Fisher, David E (2014) The melanoma revolution: from UV carcinogenesis to a new era in therapeutics. Science 346:945-9
Wagle, Nikhil; Van Allen, Eliezer M; Treacy, Daniel J et al. (2014) MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov 4:61-8
Sullivan, Ryan J; Fisher, David E (2014) Understanding the biology of melanoma and therapeutic implications. Hematol Oncol Clin North Am 28:437-53
Pop, Marius S; Stransky, Nicolas; Garvie, Colin W et al. (2014) A small molecule that binds and inhibits the ETV1 transcription factor oncoprotein. Mol Cancer Ther 13:1492-502
Chen, Hongxiang; Weng, Qing Y; Fisher, David E (2014) UV signaling pathways within the skin. J Invest Dermatol 134:2080-5
Fell, Gillian L; Robinson, Kathleen C; Mao, Jianren et al. (2014) Skin ?-endorphin mediates addiction to UV light. Cell 157:1527-34
Hsiao, Jennifer J; Fisher, David E (2014) The roles of microphthalmia-associated transcription factor and pigmentation in melanoma. Arch Biochem Biophys 563:28-34

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