Our lab is focused on the identification of genetic that can help in the diagnosis, prognostication and therapy of melanoma and related tumors. We have identified a panel of genetic changes that are characteristic of melanoma and can help distinguish it from benign tumors that mimic melanoma histologically, a finding which has been developed into a diagnostic test. We also described subtypes of melanoma which differ based on clinical, histopathological, and genetic alterations. This work has become clinically relevant as some of the genetic determinants are important for therapy stratification. For example, we discovered that certain subsets are driven by mutations in KIT, and can be treated with existing drugs. Current efforts are focused on trying to understand this unique vulnerability of some melanomas with the goal to expand it to other types. Other efforts are directed at understanding the barriers to transformation in human melanocytes. Oncogene such as BRAF or NRAS are present in benign melanocytic nevi as well as melanoma, indicating that their presence alone is insufficient for full transformation. Understanding the cooperating genetic alterations required during the progression to melanoma is expected to provide crucial insights that could be helpful diagnostically and therapeutically.
In summary, our laboratory works at the interface of clinical medicine, cutaneous oncology and pathology, with the goal to uncover critical genetic alterations in primary patient material, study their relevance using experimental model systems, and translate the results back into clinical practice.
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1. Curtin JA, Fridlyand J, Kageshita T, Patel H, Busam K, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D, Bastian BC Distinct Sets of Genetic Alterations in Melanoma. N Engl J Med. 2005 Nov 17;353(20):2135-47
2. Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, Calista D, Kanetsky PA, Pinkel D, Bastian BC. MC1R germline variants confer risk for BRAF-mutant melanoma. Science. 2006 Jul 28;313(5786):521-2.
Bauer, J., Curtin, J. A., Pinkel, D., and Bastian, B. C. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol, 2006 Aug 3.
3. Curtin, J. A., Busam, K., Pinkel, D., and Bastian, B. C. Somatic Activation of KIT in Distinct Subtypes of Melanoma J Clin Oncol, 2006 Aug 14
4. Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Garbe C, Pinkel D, Bastian BC, Improving Melanoma Classification by Integrating Genetic and Morphologic Features. PLOS Medicine, 2008 Jun 3;5(6):e12
information last updated July 2008 |
Biomedical Sciences (BMS) Graduate Program
