Uniparental Disomy in Cancer – A New Tool in Molecular Cancer


The cancer genome project has attempted to provide the complete landscape of existing mutations in tumours, but sequencing the whole genome for all tumour types is a challenging goal. Recently a novel form of abnormality in various cancers, acquired uniparental disomy (aUPD), has been revealed. aUPD regions may pinpoint the mutated genes for next generation sequencing. Therefore, identifying the aUPD regions can help to identify novel candidate genes for mutation analysis instead of randomly sequencing the genome, may help to distinguish driver genes from passenger, lead to the discovery of novel therapeutic targets and provide important prognostic information, which may thus lead to important clinical applications.

Key Concepts:

  • Acquired uniparental disomy is a novel form of abnormality in cancer.

  • The regions of acquired uniparental disomy pinpoint homozygously mutated or methylated genes.

  • Homozygously mutated genes in aUPD regions may be tumourā€suppressor or oncogenes.

  • Homozygously mutated genes in aUPD regions may be involved in tumourigenesis.

  • aUPD regions may correlate with outcome of disease, so can be of use as prognostic marker.

Keywords: acquired uniparental disomy; genome; mutation; solid tumours; leukaemia; myeloproliferative neoplasia; lymphoma

Figure 1.

Illustration depicts the normal chromosome, numeric (monosomy and trisomy) and structural (losses and gains) chromosomal rearrangements, and uniparental disomy (UPD) identified by single‐nucleotide polymorphism (SNP) array analysis (on the left panel) and illustration of homologous chromosomes in somatic cells (i.e. red chromosome represents maternal and blue chromosome represents paternal one or vice versa) (on the right panel). In the upper area of each panel, the blue line represents the average copy number signal intensity of the SNPs on the array. In the lower panel, the green and red lines show the relative signal intensity for individual homologous identified by using the AsCNAR software. (a) Depicts normal chromosome with no gains or losses, (b) loss of one copy and (c) trisomy, the gain of one copy resulting from a nondisjunction error in mitotic division. In this scenario, the cell harbours two copies of this particular chromosome from one parent, and the third homologous chromosome is from the other parent. Therefore, this change is not called uniparental disomy. aUPD, in which one copy is lost and the remaining is duplicated ((d) and (f)), or triplicate (e); therefore, all of them come from the same parent for this specific chromosome. Mechanism underlying UPD (f).



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Further Reading

Tuna M, Knuutila S and Mills GB (2009) Uniparental disomy in cancer. Trends in Molecular Medicine 15(3): 120–128. DOI: 10.1016/j.molmed.2009.01.005.

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Tuna, Musaffe, and Amos, Christopher I(May 2010) Uniparental Disomy in Cancer – A New Tool in Molecular Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022430]