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Modeling malignant melanoma in mice: pathogenesis and maintenance

Oncogene volume 18, pages 5304–5310 (1999)Cite this article

The significance and impact of melanoma as a disease entity cannot be understated. As a cancer type, incidence of melanoma is rising at a rate second only to lung cancer in women and, on its present course, the lifetime risk will reach 1 in 75 among Caucasians in the US by the year 2000 (Rigel et al., 1996). Furthermore, in contrast to most malignancies, melanoma affects a much younger population, metastasizes early in the course of the disease, and fails to respond to current therapeutic regimens (Herlyn, 1993). Presently, clinicians rely solely upon histopathologic criteria to stage melanomas, guide therapeutic decisions, and predict disease outcomes. One system, described by Breslow, measures tumor thickness from the uppermost nucleated layer of the epidermis (i.e., granular cell layer) to the greatest depth of tumor invasion. Another system, known as Clark's classification, correlates anatomic level of invasion, coupled with mitotic index, to prognosis. Such systems serve as useful prognosticators but fall short as definitive predictors of future clinical behavior of melanoma, particularly early melanocytic lesions – an ongoing problem fueled in part by the lack of diagnostic reproducibility among dermatopathologists evaluating such lesions (for review, see Barnhill et al., 1993). The inherent shortcomings of pathology-based parameters have stimulated the search for molecular markers that can predict more accurately the impending tumor phenotype, forecast disease prognosis, and ultimately guide therapeutic decisions.

Despite the long history of clinical and molecular efforts directed towards this disease, surprisingly little is known about the precise genetic lesions leading to melanoma and even more vestigial is our understanding of how the few recognized genetic lesions relate to disease classification or progression. The identification and validation of molecular markers has been hampered by practical issues such as human tissue acquisition and would undoubtedly be accelerated by the availability of a mouse model that faithfully reproduces melanoma progression on the pathological and molecular levels. Furthermore, many of the genetic lesions identified to date, with few exceptions, have come from the cytogenetic analysis of far-advanced human melanomas, particularly metastatic disease. This fact, coupled with the inherent genomic instability of malignant melanoma, emphasizes the need to utilize primary, early stage disease samples. Moreover, a better genetic roadmap of tumor progression from normal melanocyte to metastatic melanoma will be necessary in order to correlate molecular events with tumor stages. On another level, the melanoma field has a need for in vivo systems to aid in the discovery, verification and functional analysis of the growing collection of melanoma susceptibility genes.

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Acknowledgements

The author wishes to thank Drs Norman Sharpless, Nabeel Bardeesy, Ronald A DePinho for comments on the manuscript. L Chin is supported by NIH Mentored Clinician Scientist Award and the Harvard Skin Disease Center Grant. L Chin is a V Foundation Scholar.

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  1. Department of Dermatology, Department of Adult Oncology, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, M413, Boston, MA 02115, Massachusetts, USA

    Lynda Chin

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Chin, L. Modeling malignant melanoma in mice: pathogenesis and maintenance. Oncogene 18, 5304–5310 (1999). https://doi.org/10.1038/sj.onc.1203106

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