Mosaic epigenetic inheritance as a cause of early-onset colorectal cancer

Sloane, Mathew A., Nunez, Andrea C, Packham, Deborah, Kwok, Chau-To, Suthers, Graeme, Hesson, Luke B. and Ward, Robyn L. (2015) Mosaic epigenetic inheritance as a cause of early-onset colorectal cancer. JAMA Oncology, 1 7: 953-957. doi:10.1001/jamaoncol.2015.1484.


Author Sloane, Mathew A.
Nunez, Andrea C
Packham, Deborah
Kwok, Chau-To
Suthers, Graeme
Hesson, Luke B.
Ward, Robyn L.
Title Mosaic epigenetic inheritance as a cause of early-onset colorectal cancer
Journal name JAMA Oncology   Check publisher's open access policy
ISSN 2374-2445
2374-2437
Publication date 2015-10
Year available 2015
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1001/jamaoncol.2015.1484.
Open Access Status Not Open Access
Volume 1
Issue 7
Start page 953
End page 957
Total pages 5
Place of publication Chicago, IL, United States
Publisher American Medical Association
Language eng
Formatted abstract
Importance:  Constitutional hypermethylation of 1 allele throughout the soma (constitutional epimutation) is an accepted mechanism of cancer predisposition. Understanding the origin and inheritance of epimutations is important for assessing cancer risk in affected families.

Observations:  We report a 29-year-old man with early-onset colorectal cancer who showed a constitutional MLH1 epimutation (approximately 50% of alleles methylated and allele-specific loss of MLH1 expression) that was stable over a 16-year period. The epimutation was inherited without a genetic alteration from his asymptomatic mother. She showed methylation on the same allele but in less than 5% of her somatic cells.

Conclusions and Relevance:  These findings indicate that low-level somatic mosaicism for an epimutation in an asymptomatic parent can produce a nonmosaic constitutional epimutation in a child. Asymptomatic low-level methylation in some individuals may be associated with substantial cancer risk to their offspring.
Keyword Mosaic epigenetic inheritance
Early-onset colorectal cancer
Colorectal cancer
MLH1 epimutation
Low-level somatic mosaicism
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collection: School of Medicine Publications
 
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Created: Wed, 27 Jul 2016, 15:55:46 EST by Amelie Casgrain on behalf of School of Medicine