What is it about?

Cancer is a genetic disease where changes in DNA cause alterations in the control of cellular systems leading to unchecked growth. Copy number changes, including duplications, amplifications, and deletions, are a common type of DNA change observed in cancer cells but it is not always clear which of the changes are important in driving cancer development. We have examined this class of genetic alteration in prostate cancer by DNA sequencing the whole genome in 103 cancers. 64 recurrent copy number changes were detected, of which 28 were new. For genetic losses our study comprehensively assessed the role of a model called the “Knudson two-hit genetic model” where alterations in both alleles of a gene is required to generate functional alterations. This model was only supported a minor proportion of recurrent deletions (15/40). This observation indicates that other mechanisms, such haploinsufficiency and epigenetic inactivation, may account for the majority of deletions. Our studies highlight several novel changes including those in non-coding lincRNA sequences, the identification ZNF292 as a target gene for a recurrent deletion on chromosome 6, and the common Knudson deletions at the NKX3.1 loci on chromosome 8.

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Why is it important?

We find that the mechanism for "knocking-out" genes appears to be different in prostate cancer compared to other cancers. This may change the way drugs are developed to target prostate cancer. We also identify regions and genes that are commonly knocked out in cancer, which suggests they are important for the cancer to develop. This gives us greater understanding of the cancer and provides potential drug targets.


This is a comprehensive study of copy number alterations and associated point mutations in around 100 prostate cancers. We identify common alterations that seem to have an effect on the prognosis of a patient and this was validated in two other data sets which is remarkable.

Professor Daniel S. Brewer
University of East Anglia

Read the Original

This page is a summary of: Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data, PLoS Genetics, September 2017, PLOS, DOI: 10.1371/journal.pgen.1007001.
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