Inheritance of a cancer associated MLH1 germ-line epimutation

For years, the concept of DNA being the only biological unit of inheritance between generations was widely accepted (Rakyan and Beck, 2006). However, recent advances in epigenetics have exposed another component that can alter an organism’s phenotype. Epigenetics is concerned with the factors that control heritable gene expression states without altering the DNA sequence (Bird, 2007).
Hitchins et al. (2007) investigated the inheritance of a cancer associated MLH1 germ-line epimutation in humans. Hereditary nonpolyposis colorectal cancer (HNCC) is caused by germ-line sequence mutations in the mismatch repair genes MLH1 and MSH2 (Suter et al., 2004). Generally, people who have hypermethylation of one allele of MLH1 have a tendency to develop HNCC. The findings of their research indicated that the epimutation had been transmitted from a mother to her son, however, it had been erased in his spermatozoa. They also established that three other siblings, from the two families investigated, had also inherited the mutated maternal allele, yet the affected allele had reverted back to the normal state. Further research is required, however, the findings from this investigation appear to be consistent with transgenerational epigenetic inheritance and may have significant implications for future cancer susceptibility research.

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Primary Reference:
Hitchins, M.P., Wong J.J.L., Suthers, G., Suter, C.M., Martin, D.I.K., Hawkins, N.J., Ward, R.L., Inheritance of a cancer associated MLH1 germ-line epimutation, New England Journal of Medicine [New Engl. J. Med.]. Vol. 356, no. 7, pp. 697-705. 15 Feb 2007.

Secondary References:
Bird, A. 2007. Perceptions of Epigenetics, Nature, vol. 447, pp. 396-398.
Rakyan, V.K and Beck, S. 2006. Epigenetic variation and inheritance in mammals, Current Opinion in Genetics and Development, vol. 16, pp. 573-577.
Suter, C.M., Martin, D.I. and Borodin, P.M. 2004. Germline epimutation of MLH1 in individuals with multiple cancers, Nature Genetics, vol. 36, pp. 107-112.