Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. These modifications take place throughout development with subsequent events occurring later in adulthood. Recent studies, however, suggest that some epigenetic alterations that influence cancer risk are inherited through the germline from parent to child and are observed in multiple generations. Epigenetic changes may be inherited as Mendelian, non-Mendelian,

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... r environmentally induced traits. Here, we will discuss Mendelian, non-Mendelian, and environmentally induced patterns of multigenerational epigenetic alterations as well as some possible mechanisms for how these events may be occurring. [Cancer Res 2008;68(22):9116-21] Mendelian Epigenetic Inheritance CpG island methylation phenotypes in tumors are shown to positively correlate with a family history of cancer, suggesting Requests for reprints: Amanda Ewart Toland, 998 BRT, Downloaded from Figure 3 . Non-Mendelian inheritance, paramutations. One allele acts as a paramutator and epigenetically alters expression of the second allele. The epigenetic alteration persists through generations in individuals who inherit the paramutation even in the absence of the paramutator, although over time, the epigenetic state may revert and result in a milder phenotype.