Aberrations in the epigenetic phenomenon known as imprinting is a highly frequent early event in tumorigenesis (initiation of cancer) of a large number of tumors including acute myeloid leukemia (AML), Barrett’s esophagus, breast cancer, chronic myeloid leukemia (CML), colorectal cancer, esophageal cancer, Ewing’s sarcoma, glioma, laryngeal squamous cell carcinoma, hepatoblastoma, lung adenocarcinoma, meningioma, osteosarcoma, ovarian tumors, renal cell carcinoma, rhabdomyosarcoma, and Wilms’ tumor.
Imprinting is the phenomenon whereby a DNA sequence inherited from the mother, and the corresponding copy inherited from the father, have different epigenetic states (see FAQ for definition), so that only one imprinted gene, either the maternal, or the paternal copy, is active and expressed. In certain cancer predisposing conditions such as Beckwith-Wiedemann syndrome (which is accompanied with a higher frequency of Wilm’s tumor, a kidney cancer, and hepatoblastoma, a liver tumor), about half of all patients have a loss of imprinting (LOI) that leads to activation of the normally silent copy of the IGF2 growth-promoting gene, and/or to the silencing of the normally active copy of the CDKN1C growth-inhibitory gene. Either one of the two LOI events can support tumorigenesis.
Since the DNA sequences of both the maternal and paternal copy of imprinted genes are quasi-identical, it has been difficult to differentiate the parental origin of expressed imprinted genes. That is until now: a group of scientists led by Marisa Bartolomei at University of Pennsylvania School of Medicine developed a methodology that distinguishes maternal from paternal imprinted genes in any given cell using a so-called fluorescence in-situ hybridization (FISH) technique. The method is based on putting to use single nucleotide differences (about one in every 1,000 nucleotides) that exist between two individuals (in this case the mother and the father) known as single nucleotide polymorphisms (SNPs). Different fluorescent probes target different SNPs allowing to visualize (and quantify) which copy of the imprinted gene is active. This method should go a long way towards improving the early detection of loss of imprinting as a possible early epigenetic marker for many cancers (Cancer Epigenetics Society news; June 12, 2016).