Contrasting hypotheses of genomic imprinting in cancer Contrasting hypotheses of genomic imprinting in cancer. The inactivation hypothesis involves loss of expression of a tumor suppressor gene. The paternal allele is inactivated by imprinting, which displays somatic mosaicism (accounting for unilateral tumors), followed by LOH of the maternal allele (arbitrarily shown here affecting the whole chromosome). The activation hypothesis involves normal imprinting of a growth-promoting gene. Overexpression can arise from LOI of the maternal allele or UPD of the paternal allele. LOH of a distinct tumor suppressor gene would be deleterious to cell growth if it involved the transcriptionally active paternal allele of the growth-promoting gene. Alternatively, both models may be correct, with LOI and LOH leading to epigenetic silencing of a tumor suppressor gene and LOI also leading to abnormal activation of a normally silent growth-promoting gene. Dark shading, paternal chromosome; light shading, maternal chromosome, tumor suppressor gene, growth-promoting gene. (Reprinted from Feinberg AP: Genomic imprinting and gene activation in cancer. Nature Genet 4:110–113, 1993, with permission.) Source: Basic Concepts in Cancer Genetics, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: http://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch18fg1.png&sec=62651389&BookID=971&ChapterSecID=62632394&imagename= Accessed: October 31, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved