Malignant melanoma: modern black plague and genetic black box

References to ‘black cancer’ and ‘fatal black tumors with metastasis’ date to the writings of the legendary Greek physician Hippocrates in the fifth century B.C. However, it was not until the time of Napolean’s Prussian Campaign in 1806 that RenèLaennec, inventor of the stethoscope, provided the first description of melanoma as a disease entity in his presentation to the Facultéde Médecine in Paris (Bennett and Hall 1994). His 1812 manuscript reporting a case of disseminated melanoma also marks the first published use of the word ‘melanoma’ (Laennéc 1812). Several years later, a truly remarkable conceptual leap was made in the context of melanoma by a general practitioner William Norris (Norris 1820) who arrived at the conclusion that melanoma is a hereditary disease. In his 1820 manuscript, Norris wrote: ‘it is remarkable that this gentleman’s father...died of a similar disease. This tumor...originated in a mole and it is also worth mentioning that, not only my patient and his children had many moles..., but also his own father and brothers....These facts, together with a case that has come under my notice, rather similar, would incline me to believe that this disease is hereditary.’ This prescient statement is all the more striking by the fact that it was made nearly half of a century before the genetic paradigm was articulated by Gregor Johann Mendel inThe Transactions of the Brunn Natural History Society in 1866 and 1869 (see Hecht 1989).

Today, cancer biologists stand resolute in the concept that melanoma has strong genetic underpinnings. This position has been strengthened by the identification of genomic hot spots (and their resident genes) in which structural alteration correlates with the genesis and/or progression of melanoma. More recent efforts to understand the biological impact of these melanoma-associated genetic lesions have yielded a series of scientific observations …