Heritable germline epimutations in humans

Transgenerational epigenetic inheritance in health and disease

“…The methylation of the promoter occurs in the absence of underlying mutations, correlates with aberrant silencing of the tumour suppressor genes and is likely to be driving tumourigenesis [14,51 ,52,53 ]. These cases are important examples of epigenetic gene silencing in human cancer, but it remains unclear whether they are always primary epimutations [54][55][56]. The epimutation could be secondary to a genetic lesion that has occurred elsewhere in cis or in trans (Figure 1).…”

Population epigenetics

“…This problem becomes more acute when dealing with natural epigenetic variation in out-breeding species and those with limited genetic tools. These difficulties are illustrated by the discussion about whether the recently described epiallele of the human tumor suppressor locus MSH2 exhibits transgenerational inheritance [36][37][38][39]. The debate centers on whether the silenced MSH2 epiallele escapes epigenetic erasure in the transition between generations or whether it is an obligate epiallele that regains its characteristic epigenetic state in each generation on the basis of cues from underlying cis-acting genetic variation.…”

Epigenetic Regulation and Colorectal Cancer

“…60 Germline epimutation at the promoters of the DNA repair genes MLH1 and MSH2 has occasionally been detected in successive generations of some families with Lynch syndrome. 54,61,62 However, "heritable germline epimutation" should be distinguished from "transgenerational epigenetic inheritance," because these terms have different meanings.…”