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Previous Volume 356:697-705 February 15, 2007 Number 7 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Gosden, R. G. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

SUMMARY

Persons who have hypermethylation of one allele of MLH1 in somatic cells throughout the body (a germ-line epimutation) have a predisposition for the development of cancer in a pattern typical of hereditary nonpolyposis colorectal cancer. By studying the families of two such persons, we found evidence that the epimutation was transmitted from a mother to her son but was erased in his spermatozoa. The affected maternal allele was inherited by three other siblings from these two families, but in those offspring the allele had reverted to the normal active state. These findings demonstrate a novel pattern of inheritance of cancer susceptibility and are consistent with transgenerational epigenetic inheritance.

Source Information

From the Department of Medical Oncology, St. Vincent's Hospital (M.P.H., J.J.L.W., C.M.S., R.L.W.); the Schools of Medicine (M.P.H., C.M.S., R.L.W.) and Medical Sciences (J.J.L.W., N.J.H.), University of New South Wales; and the Victor Chang Cardiac Research Institute (C.M.S., D.I.K.M.) — all in Sydney; the Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, Australia (G.S.); and the Children's Hospital Oakland Research Institute, Oakland, CA (D.I.K.M.).

Address reprint requests to Dr. Ward at the Department of Medical Oncology, St. Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010, Australia, or at robyn{at}unsw.edu.au.

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