title: Inheritance of a cancer-associated MLH1 germ-line epimutation.
abstract: 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.
authors.affiliation: Department of Medical Oncology, St. Vincent's Hospital, Sydney, Australia.
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hitchins
authors.forename: Justin J L
authors.initials: JJ
authors.lastname: Wong
authors.forename: Graeme
authors.initials: G
authors.lastname: Suthers
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Suter
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hawkins
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Ward
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013094:Spermatozoa
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1