(1)
Department of Dermatology, Freiburg University Medical Center, Freiburg, Germany
Abstract
Most of the benign and all of the malignant cutaneous neoplasias can be taken as mosaic lesions. They usually reflect either loss of heterozygosity or postzygotic new mutations present in a heterozygous state. By tradition, benign melanocytic proliferations are called nevi. All other benign cutaneous neoplasias do not represent nevi. For these tumors and for some malignant neoplasias such as basal cell carcinoma, the two-hit model may not always be true. Rather, a four-mutation model of tumorigenesis may be envisaged. For other malignant skin tumors such as squamous cell carcinoma or malignant melanoma, a multistep model of carcinogenesis can be taken as certain.
At this point in time it seems reasonable to assume that most of the benign or malignant cutaneous neoplasias are mosaic lesions. As a rule, they reflect either LOH (see Sect. 10.1) or heterozygosity for a postzygotic new mutation.
By tradition, benign melanocytic proliferations are called nevi (see Sect. 7.2.1), whereas all other benign cutaneous neoplasias such as neurofibroma, lipoma, or syringoma do not represent nevi. For these tumors and for the malignant neoplasias such as basal cell carcinoma, the time-honored and simple two-hit model as first proposed by Armitage and Doll [1] and later elaborated by Knudson [10, 11], is probably not always true. Den Otter et al. [3–5] and Derkinderen et al. [6] have proposed a four-mutation model of tumorigenesis that appears to be more appropriate for many skin tumors. Recent molecular studies endorse this view [2, 8, 16, 17].
For the development of other malignant skin tumors such as squamous cell carcinoma or malignant melanoma, a multistep model of carcinogenesis can be taken as certain [7, 9, 12–15].
References
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Christiaans I, Kenter SB, Brink HC, van Os TA, Baas F, van den Munckhof P, Kidd AM, Hulsebos TJ (2011) Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. J Med Genet 48:93–97PubMedCrossRef
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