Boris Bastian

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e-mail: herlynm@wistar.org

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I first met Boris Bastian in 1994 during an evening at the Weinschänke, high above the beautiful city of Würzburg in Bavaria. He was a young attending physician, who had just completed his dermatology residency at the university and was appointed to lead the histology laboratory and ambulatory clinic. His mentor Eva Bröcker had assembled a talented and engaging group of physicians/scientists including Peter Friedl, Jürgen Becker, Eberhard Klein, Eckhardt Kaempgen, Anke Hartmann, Thomas Ruenger, and Detlev Zilikens, many of whom now hold prominent academic positions. We had spirited discussions and solved the problems of the world. Boris was literally packing to join Phil LeBoit’s dermato-pathology laboratory at UCSF for what was supposed to be a four-month stint. But, Boris also wanted to do a research project, and Phil LeBoit suggested finding a new marker for Spitz nevi. He introduced Boris to Dan Pinkel, a physicist who was leading the development of comparative genomic hybridization (CGH). Boris caught the research bug, joined Dan’s laboratory, and returned with his family to San Francisco in 1997 for a two-year research fellowship, which ultimately led to more than 13 years at UCSF.

CGH analysis of 32 melanomas that Boris brought from Wuerzburg immediately provided indications of genetic differences associated with different histologic types of melanoma and started an incredibly fruitful series of studies on many aspects of melanoma genetics that Boris is still pursuing. The excitement of the early results, including discovery of distinct genetics of melanoma and Spitz nevi, led immediately to considerable frustration as Boris’ intrinsic impatience collided with the reluctance of NIH to fund ‘discovery’ research.

Expansion of the initial CGH study to larger sets of tumors of defined histologic subtypes leads to refinement of the genetic differences among them. This theme was expanded from DNA copy number aberrations to point mutations when Boris showed that BRAF mutations, discovered at high frequency in ‘melanoma’ by Stratton and Futreal, were concentrated in melanomas arising on skin intermittently exposed to sun and were rare on skin with chronic sun damage (LMMs) and skin that was largely or completely unexposed to UV (acral and mucosal melanomas). The results were further refined in a pair of landmark papers that summarized the genetic information and then carefully integrated the genetics with elementary morphological features, thus establishing for the first time in this disease a close link between genotype and phenotype. Moreover, in collaboration with Teri Landi and her team at NCI, he linked BRAF mutations to the germline MC1R genotype.

One of the key genomic features that distinguished acral and mucosal melanomas from the other types was the presence of numerous high-level gene amplifications. By a detailed investigation into the genes in a recurrent amplification in acral melanomas, Boris was able to establish the relatively frequent occurrence of cKIT point mutations in these tumors. This discovery electrified the oncology community because imatinib (Gleevec) and related inhibitors were already approved drugs and ready for treating patients. Indeed, the patients responded dramatically, albeit permanent cures remain rare.

One of Boris’ great strengths is his ability to combine intimate clinical knowledge with basic science. This guided his very efficient experimental approach to investigating cutaneous melanomas and also has been spectacularly successful in ocular melanoma. Boris’ team discovered the GNAQ mutation in ocular melanoma, which, together with a yet unpublished mutation in the same gene family, occurs in ∼80% of all ocular melanomas, thus providing the field with new targets for therapy and raising intriguing lines for future research as to why different melanoma types have distinct lesions in the same pathways.

Boris and his family, wife Kerstin and four children aged four to eighteen, established strong roots in San Francisco. He joined the faculty in 1999 and rapidly advanced, with appointments in 2008 as Professor in Residence in Dermatology, Clinical Professor in Pathology, Leader of Cutaneous Oncology program, and Co-Director of the Center for Molecular Oncology. Despite being firmly established at UCSF, in March 2010, he moved ‘closer to Europe’ and accepted an appointment as Chairman of the Pathology Department and Member of the Human Oncology and Pathogenesis Program at the Memorial Sloan Kettering Cancer Center. To my knowledge, this is the first appointment of a dermatologist as Chair of Pathology at a major institution, and it is a testament for the broad impact his work has not just on melanoma but on all cancers. His contributions are remarkable.

We expect rapid progress as the melanoma genome atlas fills in many current gaps in our basic knowledge, hopefully allowing us to identify all of the drivers for this disease. As we know more about the genetics of melanoma, we will learn better how to use this information for prevention and for designing therapies that are substantially better than the recent dramatic successes with agents targeted to cKIT and BRAF.

Boris has been a leader in getting the melanoma field to where it is today. The recognition of his past accomplishments and the anticipation of more to come have led to his recent election as the next President of the Society for Melanoma Research.

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