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Prostate cancer genome map uncovers new DNA rearrangements

April 18, 2017

Researchers at the Garvan Institute of Medical Research in Sydney have mapped the entire genome of a prostate tumour, revealing previously undetected levels of DNA rearrangements.

The findings provide an entirely new way to view prostate cancer and information that could one day influence clinical treatment.

Most cancers are caused by small DNA mutations in a number of key genes, but prostate cancer is different to most cancers because it is more likely to be driven by complex rearrangements of DNA within the genome.

By using new technology, the study uncovered ten times more large-scale DNA rearrangements than have previously been detected in prostate cancer. Those large-scale rearrangements can include relocation of long stretches of DNA from one part of the genome to another, as well as deletions or insertions of DNA sequence at particular sites in the genome.

“Although we’ve been researching prostate cancer for many years, very little is understood about what drives these tumours,” said Professor Vanessa Hayes, Head of Garvan’s Human Comparative and Prostate Cancer Genomics Laboratory.

“One of the biggest clinical challenges is distinguishing which cancers are going to spread and become life-threatening, and which patients could be spared harsh treatment they might not need. To have any hope of targeting treatment in this way, we first need to understand the genetic drivers of each individual tumour.”

“Until now, we had no way of observing these DNA rearrangements or structural variants in prostate cancer.”

Genome sequencing and gene mapping technology reveal details

The researchers used next-generation mapping technology together with whole genome sequencing to uncover the most complete picture to date of the prostate cancer genomic landscape.

They studied a prostate tumour with a Gleason score of 7, which is the most commonly diagnosed form of prostate cancer and clinically highly unpredictable. They identified 85 large structural rearrangements, with over a third of these directly impacting on genes with known cancer-promoting potential.

“We identified 15 new potential drivers of prostate cancer,” Professor Hayes said.

“There is important synergy here with whole genome sequencing. We could not have done this with sequencing technology alone. Whole genome sequencing is invaluable in identifying small DNA mutations, but it may not detect when a gene has been completely deleted, transferred to another chromosome, or multiplied many times – which is what we see here.”

“Using next-generation mapping, we saw huge amounts of large-scale rearrangements, and genome sequencing then enabled us to identify the genes affected by these rearrangements.”

“Several cancer-promoting genes were multiplied many times, increasing their potency, and potentially driving this prostate tumour.”

The study provides proof of principle that next-generation mapping can provide insights into prostate cancer, and has future clinical potential for determining the prognosis for an individual, diagnosing prostate cancer subtypes or selecting targeted therapies.

“Whole genome sequencing opened a huge number of doors for our understanding of prostate cancer – next-generation mapping just doubled the number of doors,” said Prof Hayes.

“I believe that in the future this technology will complement next generation sequencing as a key to personalised medicine for prostate cancer.”

The study has been published recently in the journal Oncotarget. It was performed as part of the Prostate Cancer Metastasis (ProMis) program, an Australian-led international initiative.

The research was supported by the University of Sydney, The Petre Foundation, Movember and Prostate Cancer Foundation of Australia.

This news article was first published on Garvan’s website.

The Australian Cancer Research Foundation has supported cancer research at Garvan by providing three grants, totalling AUD $6.13million, towards cutting edge cancer research equipment and technology.

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